Article

Photo-Thermal Tumor Ablation in Mice Using Near-Infrared Absorbing Nanoparticles

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Abstract

The following study examines the feasibility of nanoshell-assisted photo-thermal therapy (NAPT). This technique takes advantage of the strong near infrared (NIR) absorption of nanoshells, a new class of gold nanoparticles with tunable optical absorptivities that can undergo passive extravasation from the abnormal tumor vasculature due to their nanoscale size. Tumors were grown in immune-competent mice by subcutaneous injection of murine colon carcinoma cells (CT26.WT). Polyethylene glycol (PEG) coated nanoshells (approximately 130 nm diameter) with peak optical absorption in the NIR were intravenously injected and allowed to circulate for 6 h. Tumors were then illuminated with a diode laser (808 nm, 4 W/cm2, 3 min). All such treated tumors abated and treated mice appeared healthy and tumor free >90 days later. Control animals and additional sham-treatment animals (laser treatment without nanoshell injection) were euthanized when tumors grew to a predetermined size, which occurred 6-19 days post-treatment. This simple, non-invasive procedure shows great promise as a technique for selective photo-thermal tumor ablation.

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... Noble metal NPs have attracted a considerable attention recently due to a wide range of potential applications in surface enhanced Raman scattering (SERS) [1][2][3], surface enhanced fluorescence [4][5][6], biochem- ical imaging [7][8][9], cancer treatment [7,[10][11][12], and subwavelength optical waveguides [13][14][15][16][17] among others. Noble metal NPs exhibit unique optical properties which are not found in their bulk counterparts. ...
... Understanding the influence of the temperature on the SPR in metal NPs is crucial for both pure and applied sciences of the NPs [18,22], considering recent applications of noble metal NPs in thermally assisted magnetic recording [23], thermal cancer treatment [12,[24][25][26] catalysis and nanostructure growth [27], and computer chips [28]. Additionally, understanding the underlying physics of the temperature dependence of optical properties of metal NPs is a precondition for the development of successful and reliable applications and devices. ...
... As we discussed in Section 1, the cause for such a shift is the thermal expansion of NPs. The thermal expansion leads to a decrease in the plasma bulk frequency and, in accordance with Eq. (12), to a decrease of the SPR frequency, ort the SPR red shift. Just as with the SPR broadening, when the laser wavelength approaches the SPR, the plasmon band red shift increases proving the resonant plasmonic nature of the NP heating. ...
Article
The effects of the temperature on the surface plasmon resonance (SPR) in noble metal nanoparticles at various temperatures ranging from 77 to 1190 K are reviewed. A temperature increase results in an appreciable red shift and leads to a broadening of the SPR in the nanoparticles (NPs). This observed thermal expansion along with an increase in the electron-phonon scattering rate with rising temperature emerge as the dominant physical mechanisms producing the red shift and broadening of the SPR. Strong temperature dependence of surface plasmon enhanced photoluminescence from silver (Ag) and copper (Cu) NPs is observed. The quantum photoluminescence yield of Ag nanoparticles decreases as the temperature increases, due to a decrease in the plasmon enhancement resulting from an increase in the electron-phonon scattering rate. An anomalous temperature dependence of the photoluminescence from Cu nanoparticles was also observed; the quantum yield of photoluminescence increases with the temperature. The interplay between the SPR and the interband transitions plays a critical role in this effect. The surface-plasmon involved laser heating of a dense 2D layer of gold (Au) NPs and of Au NPs in water colloids is also examined. A strong increase in the Au NP temperature occurs, when the laser frequency approaches the SPR. This finding supports the resonant plasmonic character of the laser heating of metal NPs. The sharp blue shift of the surface plasmon resonance in colloidal Au NPs at temperatures exceeding the water boiling point indicates the vapor-bubble formation near the surface of the NPs.
... The plasmonic photothermal therapy (PPTT) through use of suitable nanoparticles provides localized heat generation within a tumor within a short duration for thermal damage of the tumor [3][4][5][6]. Gold nanorods (GNRs) are widely used for plasmonic photothermal cancer therapy, due to their significant near-infrared (NIR) radiation absorption within therapeutic optical window-I from 700 to 900 nm [7][8][9][10]. The optical characteristics such as absorption and scattering coefficients of tumors are altered due to the incorporation of nanoparticles such as GNRs [11][12][13]. ...
... The wavelength of incident beam for plasmonic photothermal therapies is chosen within the optical therapeutic window (700-900 nm), where tissue constituents absorb the least amount of light [7,27]. Therefore, a diode laser of wavelength 808 nm (INFINITY Laser, New Age Instruments & Materials Pvt. ...
Article
In this study, the temporal dynamic changes in optical properties of gold nanorods (GNR) embedded tumor phantom, during photothermal interaction, are reported for plasmonic photothermal therapeutics. Tumor mimicking bilayer phantoms were prepared by using 1% agarose incorporated with 0.1% coffee powder, 0.3% intralipid solution as epidermis layer; 3% intralipid solution and 0.3% human haemoglobin (Hb) powder as dermis layer. On incorporating GNRs of concentrations 10 μg/ml, 20 μg/ml, and 40 μg/ml within the phantom, the absorption coefficients increases 4‐8 times, while there is minimal change in the reduced scattering coefficients. Further the absorption coefficient increased by ~8% with the incorporation of GNRs of concentration 40 μg/ml, while no considerable dynamic change in the optical properties is observed for the phantom embedded with GNRs of concentrations 10 μg/ml, and 20 μg/ml. The discussed results are useful for the selection of GNRs dose for pre‐treatment planning of plasmonic photothermal cancer therapeutics. https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbio.202200179
... It has a long retention duration when given intravenously into the body, especially in solid tumors. NIR irradiation can then be used to selectively ablate the nanoparticle-enhanced tumor once it has been retained in the tumor [62][63][64]. The synthetic attachment of nanoparticles with antibodies targeting to receptors overexpressed on cancer cells makes molecular specific imaging and therapy of cancer a breeze. ...
Article
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Light-induced catalysis and thermoplasmonics are promising fields creating many opportunities for innovative research. Recent advances in light-induced olefin metathesis have led to new applications in polymer and material science, but further improvements to reaction scope and efficiency are desired. Herein, we present the activation of latent ruthenium-based olefin metathesis catalysts via the photothermal response of plasmonic gold nanobipyramids. Simple synthetic control over gold nanobipyramid size results in tunable localized surface plasmon resonance bands enabling catalyst initiation with low-energy visible and infrared light. This approach was applied to the ROMP of dicyclopentadiene, affording plasmonic polymer composites with exceptional photoresponsive and mechanical properties. Moreover, this method of catalyst activation was proven to be remarkably more efficient than activation through conventional heating in all the metathesis processes tested. This study paves the way for providing a wide range of photoinduced olefin metathesis processes in particular and photoinduced latent organic reactions in general by direct photothermal activation of thermally latent catalysts. Current strategies for photoinduced olefin metathesis lack wavelength tunability. Now, plasmonic nanoparticles have been used to activate latent ruthenium catalysts, enabling light-induced olefin metathesis in the infrared range with several advantages when compared with conventional heating. Implementing this approach in ring-opening metathesis polymerization resulted in photoresponsive polymer–nanoparticle composites with enhanced mechanical properties.
... 45 The goldsilicon nanoshells were injected into mice, and continuous diode laser irradiation effectively reduced the tumor symptoms because of the strong near-infrared (NIR) absorption. 46 In addition, MR-guided focused ultrasound can reversibly disrupt the blood-brain barrier and facilitate the delivery of polystyrene NPs. 47 Notably, the application of external fields is commonly accompanied with changes in the temperature of treated tissues, which may affect NP transport and NP-cell interactions. ...
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Background: A good understanding of the adhesion behaviors of the nanocarriers in microvessels in chemo-hyperthermia synergistic therapy is conducive to nanocarrier design for targeted drug delivery. Methods: In this study, we constructed an artificial blood vessel system using gelatins with a complete endothelial monolayer formed on the inner vessel wall. The numbers of adhered NPs under different conditions were measured, as well as the interaction forces between the arginine-glycine-aspartic acid (RGD) ligands and endothelial cells. Results: The experimental results on the adhesion of ligand-coated nanoparticles (NPs) with different sizes and morphologies in the blood vessel verified that the gelatin-based artificial vessel possessed good cytocompatibility and mechanical properties, which are suitable for the investigation on NP adhesion characteristics in microvessels. When the temperature deviated from 37 °C, an increase or decrease in temperature resulted in a decrease in the number of adhered NPs, but the margination probability of NP adhesion increased at high temperatures due to the enhanced Brownian movement and flow disturbance. It is found that the effect of cooling was less than that of heating according to the observed changes in cell morphology and a decrease in cell activity under the static and perfusion culture conditions within the temperature range of 25 °C-43 °C. Furthermore, the measurement results of change in the RGD ligand-cell interaction with temperature showed good agreement with those in the number of adhered NPs. Conclusion: The Findings suggest that designing ligands that can bind to the receptor and are least susceptible to temperature variation can be an effective means to enhance drug retention.
... AuNPs can be readily synthesized and surface-modified with various biomolecules and anticancer drugs, making them potential theragnostic agents with high biocompatibility. In addition, AuNPs can convert optical energy into heat via nonradiative electron relaxation dynamics, which endows them with intense photothermal properties [11,12] Such localized heating effects can be directed toward the eradication of diseased tissue, providing a noninvasive alternative to surgery [13]. This photothermal therapy of AuNPs with a laser source has been established in the cancer therapy field [14]. ...
Article
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Gold nanoparticles (AuNPs) are cutting-edge platforms for combined diagnostic and therapeutic approaches due to their exquisite physicochemical and optical properties. Using the AuNPs physically produced by femtosecond pulsed laser ablation of bulk Au in deionized water, with a capping agent-free surface, the conjugation of functional ligands onto the AuNPs can be tunable between 0% and 100% coverage. By taking advantage of this property, AuNPs functionalized by two different types of active targeting ligands with predetermined ratios were fabricated. The quantitatively controllable conjugation to construct a mixed monolayer of multiple biological molecules at a certain ratio onto the surface of AuNPs was achieved and a chelator-free 64Cu-labeling method was developed. We report here the manufacture, radiosynthesis and bioevaluation of three different types of dual-ligand AuNPs functionalized with two distinct ligands selected from glucose, arginine–glycine–aspartate (RGD) peptide, and methotrexate (MTX) for tumor theragnosis. The preclinical evaluation demonstrated that tumor uptakes and retention of two components AuNP conjugates were higher than that of single-component AuNP conjugates. Notably, the glucose/MT- modified dual-ligand AuNP conjugates showed significant improvement in tumor uptake and retention. The novel nanoconjugates prepared in this study make it possible to integrate several modalities with a single AuNP for multimodality imaging and therapy, combining the power of chemo-, thermal- and radiation therapies together.
... Since the absorbed photon energy will be converted into heat, plasmonic resonances can be exploited to generate a local temperature increase. Such thermoplasmonic heaters have been used in, e.g., biomedical applications like innovative cancer therapy and temperature-activated drug delivery [206][207][208]. ...
... 2003, hipertermal tedavide altın parçacıklarının kullanımını detaylandıran bir hesabın ilk yayınına tanık oldu [20,30]. Meme kanseri hücrelerinin aktif olarak hedeflenmesi, hem bu çalışmada hem de Halas ve meslektaşları [21] tarafından yürütülen bir sonraki çalışmada, silika üzerinde altın nanokabukların ve HER2 antikorunun kullanılmasıyla gerçekleştirilmiştir. Bu ön araştırma, bir in vivo murin modelinde pasif hedeflemenin kullanılması yoluyla PEG kılıflı silika üzerinde altın nanokabukları konsantre etmek için vasküler erişim fenomeninin kişinin avantajına nasıl kullanılabileceğini açıklayan başka bir araştırma tarafından hızlı bir şekilde takip edildi [31] . Halas deneyinde kullanılan ve hedef bölgelerde 40 ila 508 santigrat derece sıcaklık artışına neden olan NIR ışınlaması sayesinde karsinomlar seçici olarak öldürüldü [19]. ...
Research
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Günümüzde araştırmacılar, peptit-nanopartikül konjugatlarının, sayısız hastalığın tedavisi ve teşhisi için ve ayrıca biyo-görüntüleme uygulamalarında kullanım için etkili ve güçlü araçlar olduğunu kanıtladılar. Peptit nanoparçacık konjugatlarını oluşturmak için çeşitli biyokonjugasyon teknikleri kullanılmıştır. Bu uygulamalar ilaç salınımı, hedefleme ve kanser tedavisi gibi birçok alanı içermektedir. PDC'ler olarak da bilinen peptit-ilaç konjugatları şu anda araştırılmakta ve kanser hücrelerine öldürücü ilaçların etkili ve spesifik olarak verilmesi için potansiyel bir yöntem olarak geliştirilmektedir. Peptitler, etkili bir şekilde kullanılmadan önce aşılması gereken engellerden biri olan kan, karaciğer ve böbreklerde nispeten zayıf bir stabiliteye sahiptir. Bu paradigma içinde çeşitli bozuklukların tedavisi için foto-termal terapi ve fotodinamik terapi dahil olmak üzere çeşitli teknikler kanıtlanmıştır. Ayrıca, peptit-altın nanoparçacık konjugatlarının şeklinin, boyutunun, yoğunluğunun ve protein koronasının konjugatların biyolojik aktivitesini nasıl etkilediğini gösteriyorum. Bundan sonra, peptit-AuNP konjugatlarının klinik translasyonuna yönelik beklentilerden ve şimdiye kadar karşılaşılan zorluklardan bahsedeceğim. Genel olarak, bu araştırma peptit-AuNP konjugatlarının gelecekte varoluş bozukluklarının tedavisi için terapötik ve tanısal ürünler olarak kullanılma potansiyeline sahip olduğunu ve bunların ucuz bir şekilde yapılabileceğini göstermektedir. Ders adı: Biyoteknoloji I Ders kodu: KMÜ 314
... More importantly, the absorbance can be selectively tuned to any wavelength across the visible and infrared regions of the spectrum simply by adjusting the ratio of the dielectric core to the thickness of the metal overlayer. These features render nanoshells attractive for use in technologies ranging from conducting polymer devices to biosensing and drug delivery [5][6][7]. At present, the most versatile nanoshell system is bed on the coating of silica nanoparticles with a thin layer of gold. ...
Article
Full-text available
Metal nanoshells consists of a dielectric core surrounded by a thin noble metal shell, possess unique optical properties, which render nanoshells attractive for use in different technologies. This paper reports a facile method for growth of small gold nanoparticles on the functionalized surface of larger silica nanoparticles. Mono-dispersed silica particles and gold nanoparticles were prepared by the chemical reduction method. The size of the shell nanoseeds could be altered by repeating the stage of reducing HAuCl 4 on Au/APTES/silica particles, and the time for which they react. The nanocore-shell particles prepared were studied using transmission electron microscopy (TEM), UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR) and PL spectrophotometer. The TEM images indicated that by growing gold nanoseeds over the silica cores a red shift in the maximum absorbance of UV-Visible spectroscopy is observed. Furthermore, a remarkable intensification happens in the PL spectra of silica@Au NPs in comparison with that of bare silica NPs. But, the existence of gold nanoseeds on the silica particles surfaces does not change the PL spectra peaks of these nanoparticles.
... Photothermal effect refers to the phenomenon in which thermal energy (heat) is generated when a material is excited by light, resulting in rich thermodynamic effects such as ablation, reshaping, thermal expansion, and ultrafast heating. [1][2][3][4][5][6] Thanks to the rapid development of microand nano-technology as well as being non-contact and easy to implement, the photothermal effect has applications in biomedicine, physics and chemistry, such as photothermal therapy using metallic nanoparticles, [7][8][9][10] light energy harvesting in photocatalysis, [11][12][13][14][15][16] thermal-optical data storage [17,18] and optoelectronic devices. [19][20][21][22][23] Although the photothermal effects of materials [24,25] and structures [26,27] have received much attention since the discovery of ultrafast laser heating in the last century, [28,29] there are few reports on imaging evidence of fast thermal processes in the field of photodetection. ...
Article
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Photothermal effects have recently been widely investigated for applications in the fields of biomedicine, physics and chemistry. Unfortunately, only few reports describe their potential use in ultrafast photodetectors. In this work, we provided direct evidence for ultrafast photothermal‐induced electrical behavior of a platinum microwire (Pt MW) illuminated by a focused laser beam and modulated at different frequencies (329 Hz, 10 kHz, 50 kHz and 150 kHz). The obtained electrical behavior (ΔR) images indicate that Pt‐based structures can be used to develop a new type of photodetector, namely, a photo‐thermo‐electric (PTE) detector. A high photoresponsivity of 0.3 mA/W and a fast response time of ∽ 50 µs on a single 1 µm‐wide Pt PTE detector are obtained. To further amplify the photo‐thermo‐electric effect of Pt MW, an integrated array of Pt MWs and a coating of gold nanorods (Au NRs) was combined into a hybrid PTE detector, achieving a higher responsivity close to 100 mA/W, which is 300 times higher than that of a single Pt MW PTE detector. These results confirm that Pt‐based PTE devices are promising candidates for efficient and fast‐response photodetectors. This article is protected by copyright. All rights reserved.
... Here, we show that adding a trace amount of iron oxide nanoparticles to ECM generates an improved material called ECM-n that is easily cured with a low-power laser, or incandescent light (the curing incandescent light experiment set up can be found at support information, Figure S1). This method, based on studies of laser-induced nanoparticles application in hyperthermia therapy [11][12][13][14] uses the exothermic behavior of iron oxide nanoparticles under external electromagnetic (radiofrequency, microwave, and laser) excitation. Specifically, we show that the ECM-n samples cured for 12 h under a 3W laser (808 nm wavelength) have compressive strength similar to that of ECM. ...
Article
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Preparation of construction materials on site may offer advantages in transportation and storage. However, a major limitation of on-site preparation of some materials is the need for heat and oven desiccation for adequate curing. Here, we describe a method that allows rapid curing under ambient conditions through the addition of 0.1% iron oxide nanoparticles to a carbon-negative enzymatic construction material (ECM) to make ECM-n. Specifically, we show that a low-power laser (3W at 808 nm) can cure ECM-n to an optimal mechanical strength in 12 h, which can be compared to the 14-day period needed for in situ air drying. In addition, the incorporation of nanoparticles allows rapid self-healing of large-scale flaws and that incandescent light can be used if lasers are not available. This method establishes an on-site manufacturing capability for ECM-n and other construction materials and supports thermal controllability of the local structure in low-temperature regions.
... Optical, thermal, electrical, energy, photochemical, biomedical science, and catalytic characteristics have been used to summarize the special properties of NPs [11][12][13]; these can be effectively channeled into "nano industries" for better and more environmentally friendly industrial uses that safeguard biological life [14]. An intriguing field in nanoscience and technology during the past ten years has been innovative approaches/methods for the synthesis of nanomaterials (such as metal nanoparticles such as graphene, and its composites, quantum dots (QDs), carbon nanotubes (CNTs), Pd, Cu [15][16][17][18][19][20][21][22][23][24][25][26][27][28]. By conjugating nanoparticles with targeting ligands, it is possible to direct their accumulation to specific parenchymal areas, such as tumor regions, in the body. ...
Article
In recent years, the green synthesis of hybrid nanoparticles has become a cutting-edge and fascinating field of research. As compared to hybrid NPs made using traditional techniques, numerous studies show the significant benefits of combination NPs synthesized via the greener pathway utilizing natural resources such as plants, including the removal of toxic pollutants, the reduction of following complicated chemical synthesis, environmentally friendly nature, cost-effective, convenient, dependable, affordability, stability and easy way to synthesize. Because of these established benefits, great effort is being made to apply green synthesis processes. We enter a newly developed advanced organic/inorganic hybrid nanomaterials data table in this research to look for extracts type, preparation time, temperature, morphology, size, color, and medical applications. The morphology, composition, size, and color of smart organic/inorganic hybrid nanoparticles were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, the antimicrobial, anticancer, and cytotoxicity effects of these hybrid nanoparticles on various bacteria, cancer cells, and normal human cells are discussed. Excellent performances were reported in different literature. Green synthesized hybrid nanoparticles for multimodal imaging have potential application in biomedical research to replace the traditional techniques and materials. Functional hybrid nanomaterials have the potential to be utilized in numerous biomedical disciplines as advanced biomaterials with the ultimate objective of effectively detecting and treating a variety of human diseases with a higher success rate.
... Optical, thermal, electrical, energy, photochemical, biomedical science, and catalytic characteristics have been used to summarize the special properties of NPs [11][12][13]; these can be effectively channeled into "nano industries" for better and more environmentally friendly industrial uses that safeguard biological life [14]. An intriguing field in nanoscience and technology during the past ten years has been innovative approaches/methods for the synthesis of nanomaterials (such as metal nanoparticles such as graphene, and its composites, quantum dots (QDs), carbon nanotubes (CNTs), Pd, Cu [15][16][17][18][19][20][21][22][23][24][25][26][27][28]. By conjugating nanoparticles with targeting ligands, it is possible to direct their accumulation to specific parenchymal areas, such as tumor regions, in the body. ...
... Due to inhomogeneous and uncontrolled labeling, there is a loss of information and generation of artifacts that offer false impressions generating erroneous data [28]. Previously, absorption-based photothermal imaging [29], single-and twophoton luminescence [30], and defocused imaging [31] methods were used to study the orientation of a single nanoparticle. In previous studies, a laser was utilized, and wherein laser generates heat which creates possibilities of thermal deformation [32] and limits applications in biology/soft matters. ...
Article
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Rotational dynamics at the molecular level could provide additional data regarding protein diffusion and cytoskeleton formation at the cellular level. Due to the isotropic emission pattern of fluorescence molecules, it is challenging to extract rotational information from them during imaging. Metal nanoparticles show a polarization-dependent response and could be used for sensing rotational motion. Nanoparticles as an orientation sensing probe offer bio-compatibility and robustness against photo-blinking and photo-bleaching compared to conventional fluorescent molecules. Previously, asymmetric geometrical structures such as nanorods have been used for orientational imaging. Here, we show orientational imaging of symmetric geometrical structures such as 100 nm isolated silver nanocubes by coupling a hyperspectral detector and a focused ion beam (FIB)-fabricated correlating substrate. More than 100 nanocubes are analyzed to confirm spectral shifts in the scattering spectra due to variations in the orientation of the nanocubes with respect to the incoming light. Results are further validated using finite-difference time-domain simulations. Our observations suggest a novel strategy for high-throughput orientation imaging of nanoparticles.
... While early studies used direct injections of GNSs into subcutaneous tumors, later studies found that intravenously delivered GNSs combined in tumors as soon as 6 h after inoculation. Treatment of these mice with an 800 MW, NIR (Near Infrared) laser spouting at 808 nm, at 4 W= cm 2 for 3 min resulted in a substantial survival difference compared to non-radiated mice [22]. When gold Nano-particles are earnestly intended to tumors in mice, they improve survival compared to passively targeted nanoparticles [23,24]. ...
Article
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Cancer is clearly a major cause of disease and fatality around the world, yet little is known about how it starts and spreads. In this study, a model in mathematical form of breast cancer guided by a system of (ODE’S) ordinary differential equations is studied in depth to examine the thermal effects of various shape nanoparticles on breast cancer hyperthermia therapy in the existence of a porous media with fractional derivative connection, when utilizing microwave radiative heating. The unsteady state is determined precisely using the Laplace transform approach to crop a more decisive examination of temperature dissemination of blood temperature inside the breast tissues. Durbin's and Zakian's techniques are used to find Laplace inversion. Mild temperature hyperthermia is used in the treatment, which promotes cell death by increasing cell nervousness to radiation therapy and flow of blood in tumor. In the graphical findings, we can witness the distinct behavior of hyperthermia therapy on tumor cells by applying various metabolic heat generation rates across various time intervals to attain the optimal therapeutic temperature point. Particularly, we used graphs to visualize the behavior of different Nanoparticles with different shaped during hypothermia therapy. In comparison to other nanoparticles and shapes, it demonstrates that gold nanoparticles with a platelet shape are the best option for improving heat transmission. Which assess of heat transfer up to 16.412%.
... Aer excitation with a NIR laser, Au NRs released heat into the tumor environment, resulting in the rupture of the tumor cell membrane. 228 Aer that, Huang et al. reported that Au NRs with a low aspect ratio can be used as a simultaneous imaging and therapeutic agent to promote tumor cell recognition and photothermal removal in vitro due to their strong scattering and absorption properties in NIR spectroscopy. 229 The demonstration greatly increases the interest in the treatment and diagnosis of certain cancers using Au NRs. ...
Article
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Noble metal nanomaterials with special physical and chemical properties have attracted considerable attention in the past decades. In particular, Au nanocrystals (NCs), which possess high chemical inertness and unique surface plasmon resonance (SPR), have attracted extensive research interest. In this study, we review the properties and preparation of Au NCs with different morphologies as well as their important applications in biological detection. The preparation of Au NCs with different shapes by many methods such as seed-mediated growth method, seedless synthesis, polyol process, ultrasonic method, and hydrothermal treatment has already been introduced. In the seed-mediated growth method, the influence factors in determining the final shape of Au NCs are discussed. Au NCs, which show significant size-dependent color differences are proposed for preparing biological probes to detect biomacromolecules such as DNA and protein, while probe conjugate molecules serves as unique coupling agents with a target. Particularly, Au nanorods (NRs) have some unique advantages in the application of biological probes and photothermal cancer therapy compared to Au nanoparticles (NPs).
... For plasmonic photothermal therapeutics, an incident light wavelength is chosen within the optical therapeutic window, i.e., 700-900 nm within which tissue constituents possess minimum absorption (O'Neal et al. 2004;Bashkatov et al. 2018). Accordingly, 808 nm laser diode (INFINITY Laser, New Age Instruments & Materials Pvt. ...
Article
Plasmonic photothermal cancer therapeutics utilize localized heat generation for thermal damage of a tumor. Here, the spatial distribution of energy in the incident electromagnetic wave will influence the photothermal temperatures within the tumor. Therefore, for a nanoparticle concentration attained within a tumor, the shape of the incident optical beam presents a better option to control the spatiotemporal heat confinement and thus thermal damage of a tumor. In this article, three beam shapes, i.e., Gaussian, Microlens array (MLA) beam, and annular beam were generated from 808 nm laser using optical elements, such as microlens array and axicon lens. The spatiotemporal photothermal temperatures (axial and radial distribution) were evaluated experimentally through gold nanorods (GNRs) embedded tumor phantoms. Irradiation intensity was chosen as 1 W/cm2 for an exposure duration of 900 s. Results show that the annular beam yields 19 and 30% wider surface temperature zones (temperature rise ≥ 10 °C) as compared to Gaussian and MLA beams, respectively. Regarding the axial temperature distribution, the Gaussian beam provides about 7 and 17% higher temperature rise (at 2 mm depth) as compared to MLA and annular beam. On increasing the GNR concentration from 10 to 40 µg/ml, the temperature is enhanced by 30 and 120% at depths of 2 and 7 mm, respectively, for the beam shapes. Overall, the annular beam provides uniform photothermal temperatures with wider elevated temperature zones radially as well as along the phantom depth. In addition, the temperature increases uniformly over the entire zone for higher irradiation durations. The discussed spatiotemporal photothermal temperatures for different beam shapes provide useful insights for the selection of an incident beam shape for further studies toward plasmonic photothermal cancer therapeutics. https://rdcu.be/cTrkq
... The FDA organization has approved the conjugation of anticancer drugs, diagnostic agents, and/or targeting agents to nanobiomaterials to build nanostructure weapons against cancer cells 2 . At the time being, AuNPs are prepared by different green and synthetic techniques with different shapes as nanospheres, nanorods, nanocubes, nanobranches, nanobipyramids, nanoflowers, nanoshells, nanowires, and nanocages 47,48 . Green chemistry is one of the promising research areas in nanotechnology for the fabrication of nanomaterials due to the growing demand to the synthesis of environmentally safe nanomaterials 49 and to reduce the cost and energy consumption associated with the production process using the physical/chemical techniques 50 . ...
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Biosynthesis of gold nanoparticles (AuNPs) using algal polysaccharides is a simple, low-cost, and an eco-friendly approach. In the current study, different concentrations of Arthospira platensis exopolysaccharides (EPS) were used to synthetize AuNPs via the reduction of gold ions. The biologically synthesized AuNPs (AuNPs1, AuNPs2, AuNPs3) were prepared in 3 different forms through the utilization of three different ratios of EPS-reducing agents. AuNPs analysis confirmed the spherical shape of the EPS-coated AuNPs. Furthermore, AuNPs prepared by EPS and l-ascorbic acid (AuNPs3) showed more stability than the AuNPs colloidal solution that was prepared using only l-ascorbic acid. Analysis of the antimicrobial effects of AuNPs showed that E. coli was the most sensitive bacterial species for AuNPs3 and AuNPs1 with inhibition percentages of 88.92 and 83.13%, respectively. Also, safety assay results revealed that AuNPs3 was the safest biogenic AuNPs for the tested noncancerous cell line. The anticancer assays of the biogenic AuNPs1, AuNPs2, and AuNPs3 against MCF-7 cell line indicated that this cell line was the most sensitive cell line to all treatments and it showed inhibition percentages of 66.2%, 57.3%, and 70.2% to the three tested AuNPs, respectively. The AuNPs also showed abilities to arrest MCF-7 cells in the S phase (77.34%) and increased the cellular population in the sub G0 phase. Gene expression analysis showed that AuNPs3 down regulated Bcl2, Ikapα, and Survivn genes in MCF-7 treated-cells. Also, transmission electron microscopy (TEM) analysis of MCf-7 cells revealed that AuNPs 3 and AuNPs2 were localized in cell vacuoles, cytoplasm, and perinuclear region.
... Nanotechnology has attained attention in medical sciences because of its role in plant, animal, and human health which led to many applications in the field of medicine [1,8]. Examples of these include controlled delivery of drugs, electroluminescent, imaging, detection, destruction of tumor, cancer diagnosis, and tissue engineering [9][10][11][12][13][14][15]. ...
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The synthesis of metal nanoparticles by using plant extracts is previously explored in phytomedicines. Nanobiotechnology has many applications, including cosmetic, packing, coating, biomedicine, and enhanced biological activity. Keeping in view the importance of Pistacia chinensis, its gold nanoparticles (AuNPs) have been synthesized by the eco-friendless and cost-effective method. In this study, the synthesized nanoparticles were characterized by advanced techniques such as UV-visible spectroscopy, Fourier transform infrared (FT-IR), and atomic force microscope (AFM) analysis. The biological activities of these synthesized nanoparticles were examined in vitro by measuring the enzymatic inhibition potential on urease and carbonic anhydrase and in vivo by determining the analgesic and sedative activities. The UV spectrum indicated various peaks at the range of 530-550 nm, showing nanoparticles formation. The FT-IR spectroscopy of the extracts and AuNPs indicated the presence of NH, C═N, and N═O in the extract involved in the nanoparticles synthesis. The size of nanoparticles was determined by AFM analysis. The AFM showed that the nanoparticles range from 10 to 100 nm and are almost spherical in shape. The synthesized AuNPs exhibited significant urease inhibition potential with an IC50 value of 44.98. Similarly, the nanoparticles exhibited good carbonic anhydrase inhibition with an IC50 value of 53.54 against acetazolamide having IC50 0.13. Pistacia chinensis extract and its AuNPs exhibited excellent attenuation p < 0.01 in acetic acid-induced writhing model at a dose of 15 mg/kg. The synthesized nanoparticles showed a significant sedative effect p < 0.001 compared to the standard drug. This research work has developed a green method to synthesize nanoparticles by using Pistacia chinensis extract and directed the researcher to purify active phytochemicals from Pistacia chinensis involved in nanoparticles synthesized.
... PTT is emerging as an adjuvant and alternative approach for cancer therapy. [6][7][8][9][10][11][12] The Halas group recently reported a pilot study that demonstrated successful focal laser ablation in 15 of 16 patients affected with low or intermediate-risk localized prostate cancer, using gold nanoshells in conjunction with magnetic resonance and ultrasound fusion imaging. 13 Imaging in PTT plays a critical role in identifying nanoparticle accumulation, precise location, and tumour morphology, allowing for spatial and temporal control of NIR light irradiation. ...
Article
This study reports a hybrid lipo-polymeric nanosystem (PDPC NPs) synthesized by a modified hydrogel-isolation technique. The ability of the nanosystem to encapsulate hydrophilic and hydrophobic molecules has been demonstrated, and their enhanced cellular uptake has been observed in vitro. The PDPC NPs, surface coated with gold by in situ reduction of chloroauric acid (PDPC-Au NPs), showed a photothermal transduction efficacy of ∼65%. The PDPC-Au NPs demonstrated an increase in intracellular ROS, triggered DNA damage and resulted in apoptotic cell death when tested against breast cancer cells (MCF-7). The disintegration of PDPC-Au NPs into smaller nanoparticles with near-infrared (NIR) laser irradiation was understood using transmission electron microscopy imaging. The lipo-polymeric hybrid nanosystem exhibited plasmon-enhanced fluorescence when loaded with IR780 (a NIR dye), followed by surface coating with gold (PDPC-IR-Au NPs). This paper is one of the first reports on the plasmon-enhanced fluorescence within a nanosystem by simple surface coating of Au, to the best of our knowledge. This plasmon-enhanced fluorescence was unique to the lipo-polymeric hybrid system, as the same was not observed with a liposomal nanosystem. The plasmon-enhanced fluorescence of PDPC-IR-Au NPs, when applied for imaging cancer cells and zebrafish embryos, showed a strong fluorescence signal at minimal concentrations of the dye. The PDPC-IR-Au NPs were also applied for photothermal therapy of breast cancer in vitro and in vivo, and the results depicted significant therapeutic benefits.
... Nanopartikel emas banyak dipelajari karena termasuk salah satu nanopartikel yang paling stabil, tidak beracun, dan mudah disintesis [8]. Berbagai ukuran, bentuk dan struktur nanopartikel emas banyak dianalisis seperti nanospheres, nanorods, nanocubes, nano branches, nanobipyramid, nanoflowers, nanoshells, nanowires, dan nanocages dengan berbagai teknik [9][10] [11]. ...
Article
Pada review ini dibahas mengenai sintesis nanopartikel emas atau Au-NPS. Nanopartikel merupakan kumpulan atom, ion, atau molekul yang umumnya berukuran 1-100 nm sehingga nanopartikel emas merupakan nanopartikel dari logam emas. Nanopartikel dikembangkan salah satunya dimanfaatkan dalam bidang kesehatan sebagai penghantar obat, terapi fotodinamik, terapi fototermal, biosensor. Nanopartikel emas merupakan salah satu nanopartikel yang paling stabil, tidak beracun, dan mudah disintesis. Nanopartikel emas dapat disintesis melalui metode kimia, metode seeded growth, metode fisika, metode biologi, metode digestive ripening, metode elektrokimia, dan metode sonokimia sehingga dihasilkan nanopartikel emas dengan berbagai ukuran, bentuk, dan struktur. Nanopartikel berukuran 1-100 nm; berbentuk bulat, batang,
... Nanopartikel emas banyak dipelajari karena termasuk salah satu nanopartikel yang paling stabil, tidak beracun, dan mudah disintesis [8]. Berbagai ukuran, bentuk dan struktur nanopartikel emas banyak dianalisis seperti nanospheres, nanorods, nanocubes, nano branches, nanobipyramid, nanoflowers, nanoshells, nanowires, dan nanocages dengan berbagai teknik [9][10] [11]. ...
Article
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Pada review ini dibahas mengenai sintesis nanopartikel emas atau Au-NPS. Nanopartikel merupakan kumpulan atom, ion, atau molekul yang umumnya berukuran 1-100 nm sehingga nanopartikel emas merupakan nanopartikel dari logam emas. Nanopartikel dikembangkan salah satunya dimanfaatkan dalam bidang kesehatan sebagai penghantar obat, terapi fotodinamik, terapi fototermal, biosensor. Nanopartikel emas merupakan salah satu nanopartikel yang paling stabil, tidak beracun, dan mudah disintesis. Nanopartikel emas dapat disintesis melalui metode kimia, metode seeded growth, metode fisika, metode biologi, metode digestive ripening, metode elektrokimia, dan metode sonokimia sehingga dihasilkan nanopartikel emas dengan berbagai ukuran, bentuk, dan struktur. Nanopartikel berukuran 1-100 nm; berbentuk bulat, batang,
... Nanopartikel emas banyak dipelajari karena termasuk salah satu nanopartikel yang paling stabil, tidak beracun, dan mudah disintesis [8]. Berbagai ukuran, bentuk dan struktur nanopartikel emas banyak dianalisis seperti nanospheres, nanorods, nanocubes, nano branches, nanobipyramid, nanoflowers, nanoshells, nanowires, dan nanocages dengan berbagai teknik [9][10] [11]. ...
Article
Pada review ini dibahas mengenai sintesis nanopartikel emas atau Au-NPS. Nanopartikel merupakan kumpulan atom, ion, atau molekul yang umumnya berukuran 1-100 nm sehingga nanopartikel emas merupakan nanopartikel dari logam emas. Nanopartikel dikembangkan salah satunya dimanfaatkan dalam bidang kesehatan sebagai penghantar obat, terapi fotodinamik, terapi fototermal, biosensor. Nanopartikel emas merupakan salah satu nanopartikel yang paling stabil, tidak beracun, dan mudah disintesis. Nanopartikel emas dapat disintesis melalui metode kimia, metode seeded growth, metode fisika, metode biologi, metode digestive ripening, metode elektrokimia, dan metode sonokimia sehingga dihasilkan nanopartikel emas dengan berbagai ukuran, bentuk, dan struktur. Nanopartikel berukuran 1- 100 nm; berbentuk bulat, batang, segitiga, kubus, oktahedral, dan polihedral; berstruktur nanospheres, nanorods, nanocubes, nano branches, nanobipyramid, nanoflowers, nanoshells, nanowires, dan nanocages. Kata kunci : aplikasi, emas, nanopartikel, sintesis.
... Following the exposure of the GNR treated malignant cells to a continuous Ti:Sapphire red laser at 800 nm, significant photothermal damage was reported for both malignant cell lines requiring half the laser energy compared with nontargeted GNPs based on the increased cellular uptake of GNRs. In another study, Halas et al [18][19][20][21]. achieved cell death using gold nanoshells with LSPR in the NIR region through passive and active cancer targeting using PEG-conjugated nanoshells and anti-Her2 conjugated nanoshells, respectively. ...
Article
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Gold nanoparticles (GNPs) have served as an excellent candidate for biomedical applications. GNPs can be conjugated with carboxyl-polyethylene glycol-thiol (PEG) as a stealth coating which prolongs circulation time1, 2 and increases cellular uptake.3-6 To examine the biological effects of PEG-coated GNPs, we investigated their cytotoxicity on human cervical cancer C33A cells as compared to citrate-capped GNPs. Our results indicated that PEGylated GNPs markedly induce apoptosis and necrosis causing cell shrinkage and cell membrane asymmetry. 30 nm citrate-capped GNPs were synthesized in aqueous solution using a citrate-reduction method. GNPs were functionalized with PEG (MW = 7500 g mol-1. The GNPs were characterized using scanning electron microscopy (SEM), confirming that the as-synthesized GNPs have a diameter of 30 nm. Dynamic light scattering (DLS) determined that the hydrodynamic diameter of PEGylated GNPs was 78.82 nm, and that of citrate-capped GNPs was 43.82 nm. Zeta potential measurements showed an increase in colloidal stability for PEGylated GNPs as compared to citrate GNPs, with a zeta potential of -33.33 mV observed for citrate-capped GNPs and a zeta potential of -43.38 mV observed for PEGylated GNPs. The PEGylated GNPs were found to effectively induce early and late-stage apoptosis in C33A cells with a significant reduction in total cell viability of 32.3%. Based on the apoptotic activity in C33A cells, PEGylated GNPs may serve as a promising radiosensitizer for cancer treatments.
... Near-infrared (NIR) laser is an ideal light source for performing PTT, because the NIR region is a transparency window for biological tissues [13] Under the illumination of a NIR laser, functional nanomaterials are considered to be excellent photothermal transduction agents (PTAs), which can efficiently harvest NIR photons and produce heat to induce localized hyperthermia. PTT mainly utilizes the photothermal effect of PTAs to kill cancer cells and ablate tumors [14][15][16]. Compared with other therapeutic strategies, PTT has several advantages, including non-invasiveness, low side effects, and high efficiency [17][18][19][20][21]. ...
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Photothermal therapy (PTT) has become an important therapeutic strategy in the treatment of cancer. However, exploring novel photothermal nanomaterials with satisfactory biocompatibility, high photothermal conversion efficiency, and efficient theranostic outcomes, remains a major challenge for satisfying clinical application. In this study, poly-ethylene glycol modified rhenium disulfide (PEG-ReS2) nanosheets are constructed by a simple-liquid phase exfoliation method. The PEG-ReS2 nanosheets were demonstrated to have good solubility, good biocompatibility, low toxicity, and strong capability of accumulating near-infrared (NIR) photons. Under 808 nm laser irradiation, the PEG-ReS2 nanosheets were found to have an excellent photothermal conversion efficiency (PTCE) of 42%. Moreover, the PEG-ReS2 nanosheets were demonstrated to be ideal photothermal transduction agents (PTAs), which promoted rapid cancer cell death in vitro and efficiently ablated tumors in vivo. Interestingly, the potential utility of up-regulation or down-regulation of miRNAs was proposed to evaluate the therapeutic outcomes of PEG-ReS2 nanosheets. The expression levels of a set of miRNAs in tumor-bearing mice were restored to normal levels after PTT therapy with PEG-ReS2 nanosheets. Both down-regulation miRNAs (miR-125a-5p, miR-34a-5p, miR-132-3p, and miR-148b-3p) and up-regulation miRNAs (miR-133a-3p, miR-200c-5p, miR-9-3p, and miR-150-3p) were suggested to be important clinical biomarkers for evaluating therapeutic outcomes of breast cancer-related PTT. This work highlights the great significance of PEG-ReS2 nanosheets as therapeutic nanoagents for cancer therapy.
... Plasmonic particles have attracted considerable interest in biomedical, 1 sensing, 2−4 catalysis, 5−7 light conversion, 8 and photothermal 9 applications. The performance of a plasmonic material depends significantly on the intensity of plasmonic absorption. ...
... We analyze the influence of the laser pulse width and show that it is related to the attenuation rate of the acoustic field. We demonstrate an optimal laser pulse width of 0.01 ns to 10.44 ns depending on the nanorod dimension. We further provide a design principle of the nanorod's dimension and material composition (coating) to achieve an optimal near-field photoacoustic amplitude As illustrated in Fig. 1a, a pulsed laser illuminates a gold nanorod to generate near-field photoacoustic pressure. ...
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When gold nanorods are molecularly targeted to cells, they can act as nanoscale transducers that amplify the acoustic signals triggered by light, known as the photoacoustic effect. However, the majority of the existing studies focus on the far field photoacoustic signals that can be measured with an ultrasound transducer, much less is known in the near field regime where the photoacoustic signal strongly interacts with the cells and cell membrane molecules. Here we discuss the theory and numerical studies of near field photoacoustic distribution generated by a single gold nanorod upon pulsed laser illumination. Our results show that the near field region is much smaller than the wavelength of the associated acoustic pulse, and has a distinct spatial distribution controlled by the geometry of the nanorod. Specifically, the near field photoacoustic distribution of the nanorod is anisotropic and converges to an isotropic spherical wave at 100 nm away from the nanorod surface. Immediately around the nanorod, the near field photoacoustic signals decay dramatically, depending on the orientation. The nanorod shows about 75 percent stronger photoacoustic signal amplitude in the transverse direction than in the longitudinal direction. We show that the spatial confinement of the photoacoustic signal is also related to the laser pulse width and identify an optimal pulse width in the range of 0.01 ns to 10.44 ns depending on the nanorod dimension.
... Nanoshells can be used for photo-thermal ablation of tumor tissue or cells, and it was confirmed in both murine models in vivo and human breast carcinoma cells in vitro [65,69]. Nanoshells' spherical and layered nanoparticles consist of dielectric silica (SiO2) core coated with a thin metal shell FIGURE 17.6 (C) Schematic of a nanowire device configured as a sensor with antibody receptors (green) and binding a protein with net negative charge yields an increase in the conductance. ...
Chapter
At present, real-time, personalized, highly selective, and sensitive early-stage treatment of various diseases remains a significant challenge for the modern chemist. The ability to interact with nanomaterials and the development of nanotechnology-based therapies could potentially extend molecular and subcellular detection beyond the limits of conventional diagnostic modalities. Nanotechnology, a new era in medicinal and modern chemistry, dramatically accelerates the discovery of biomarkers and detection of various diseases, especially cancer. This chapter summarizes several of the most promising nanomaterials and nanodevices and their applications in the early-stage detection of cancer cell lines. Various nanodevices are reviewed, including several examples of current research and commercially available devices. Advances in nano-based cancer cell detection and drug delivery offer great freedom and improve the quality of patient life.
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Allyl monomers that were previously considered to be difficult to polymerize are applied, and Fe3O4@polydiallyl isophthalate (Fe3O4@PDAIP) magnetic were synthesized by one-step photopolymerization. The skeleton of the microspheres is made of diallyl isophthalate (DAIP). We obtained the microspheres using the photo-click technique in a soft template with Nano-Fe3O4 evenly disseminated in hydrophobic DAIP by cation-π and polar interaction. The obtained Fe3O4@PDAIP magnetic microspheres can achieve tumor cell necrosis temperatures (41-52 ℃) in an alternating magnetic field due to their inherent magnetic response. The results of in vitro CT and MR imaging indicate that the microspheres might be monitored accurately in vivo. Then the structural characteristics of the microspheres were confirmed by morphological analysis and physicochemical property analysis. Experiments in vitro and in vivo revealed that the microspheres had an anti-tumor effect and their biocompatibility satisfies the standards. The stability experiment proves that the microspheres have the potential for long-term effectiveness in vivo. It demonstrates the promise of Fe3O4@PDAIP magnetic microspheres in clinical applications.
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All-optical nanothermometry has become a powerful, remote tool for measuring nanoscale temperatures in applications ranging from medicine to nano-optics and solid-state nanodevices. The key features of any candidate nanothermometer are brightness, sensitivity, and (signal, spatial, and temporal) resolution. Here, we demonstrate a real-time, diamond-based nanothermometry technique with excellent sensitivity (1.8% K-1) and record-high resolution (5.8 × 104 K Hz-1/2 W cm-2) based on codoped nanodiamonds. The distinct performance of our approach stems from two factors: (i) temperature sensors─nanodiamonds cohosting two group IV color centers─engineered to emit spectrally separated Stokes and anti-Stokes fluorescence signals under excitation by a single laser source and (ii) a parallel detection scheme based on filtering optics and high-sensitivity photon counters for fast readout. We demonstrate the performance of our method by monitoring temporal changes in the local temperature of a microcircuit and a MoTe2 field-effect transistor. Our work advances a powerful, alternative strategy for time-resolved temperature monitoring and mapping of micro-/nanoscale devices such as microfluidic channels, nanophotonic circuits, and nanoelectronic devices, as well as complex biological environments such as tissues and cells.
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Light-matter interactions are often considered governed by the electric optical field only, leaving aside the magnetic component of light. However, the magnetic part plays a determining role in many optical processes from light and chiral-matter interactions, photon-avalanching to forbidden photochemistry, making the manipulation of magnetic processes extremely relevant. Here, by creating a standing wave using a plasmonic nanomirror we manipulate the spatial distributions of the electric and magnetic fields and their associated local density of states, allowing the selective control of the excitation and emission of electric and magnetic dipolar transitions. This control allows us to image, in 3D, the electric and magnetic nodes and anti-nodes of the fields interference pattern. It also enables us to enhance specifically photoluminescence from quantum emitters excited only by the magnetic field, and to manipulate their quantum environment by acting on the excitation fields solely, demonstrating full control of magnetic and electric light-matter interactions.
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Silica-Gold Nanostructures (SGNs), composed of a silica core decorated by gold nanoparticles, have the photothermal capacity to transform near-infrared (NIR) wavelengths into heat. This work presents a simple, efficient, and replicable method of synthesis of SGNs and their characterization by: (1) transmission electron microscopy to obtain micrographs of the particles and their corresponding diameter distribution; (2) diffraction patterns showing the amorphous atomic arraignment of the silica and the crystalline atomic arrangement of the gold nanoparticles; (3) zeta potential confirming the stability of the SGNs in a colloidal solution; and (4) thermal images displaying the capacity of SGNs to convert NIR irradiation into heat and their respective increment in temperature. SGNs were synthesized over silica cores with diameters of 63, 83, and 132 nm and decorated with a partial gold shell. They were heated with a coherent light intensity of 340 mW/cm2 with a wavelength of 852 nm. This wavelength is within the range of the optical window of the human body; therefore, SGNs may be used for the photothermal ablation of tumors with no damage to the tissue. The heating of different dimensions of SGNs took 6-8 min of NIR radiation, and their cooling, once the laser was turned off, was in the order of 2-3 min. It was found that SGNs, with a core diameter of 132 nm, have a notable photothermal capacity. That enables them to increase the temperature of their surroundings by 4.4 ºC. This increment in temperature is sufficient to induce cellular necrosis, which makes SGNs a good option for photothermal treatments.
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The focus of this present investigation is to examine the heating characteristics of gold and silver nanoparticles at different laser wavelengths. Comparative research on the heat transfer studies with gold ultrafine particles and silver ultrafine particles was undertaken to determine an appropriate frequency and substance with greater photothermic effectiveness for hyperthermic use in cancer therapy. At 488 nm and 540 nm, gold nanoparticles are found to be greater photothermally efficient than silver nanoparticles. The 540 nm laser burns gold nanoparticles greater than the 488 nm laser. Silver nanoparticles, on the other hand, showed a slightly lower temperature increase at 540 nm than at 488 nm. In the diametral surface range of 0–50 nm, size‐dependent impact research showed that the absorbance effectiveness of single gold nanoparticulate with larger diameters is larger than those with lower diameters.
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With the rapid growth of the research content of nanomaterials and tumor immunity, the hot spots and urgent problems in the field become blurred. In this review, noticing the great development potential of this research field, we collected and sorted out the research articles from The Clarivate Analytics Web of Science (WOS) Core Collection database in the field over the past 20 years. Next, we use Excel 2019 from Microsoft (Microsoft Corp, Redmond,WA, USA), VOSviewer (version 1.6.18, Leiden University, Leiden, Netherlands), CiteSpace (Chaomei Chen, Drexel University, USA) and other softwares to conduct bibliometric analysis on the screened literatures. This paper not only analyzes the countries, institutions and authors with outstanding contributions in the current research field, but also comes up with the hot spots of current research. We hope that by analyzing and sorting out the past data, we can provide help for the current clinical work and future scientific research.
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This paper presents a discontinuous Galerkin (DG) integral equation (IE) method for the electromagnetic analysis of arbitrarily-shaped plasmonic assemblies. The use of nonconformal meshes provides improved flexibility for CAD prototyping and tessellation of the input geometry. The formulation can readily address nonconformal multi-material junctions (where three or more material regions meet), allowing to set very different mesh sizes depending on the material properties of the different subsystems. It also enables the use of h-refinement techniques to improve accuracy without burdening the computational cost. The continuity of the equivalent electric and magnetic surface currents across the junction contours is enforced by a combination of boundary conditions and local, weakly imposed, interior penalties within the junction regions. A comprehensive study is made to compare the performance of different IE-DG alternatives applied to plasmonics. The numerical experiments conducted validate the accuracy and versatility of this formulation for the resolution of complex nanoparticle assemblies.
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Photothermal therapy using nanoparticles is a prominent technique for cancer treatment. The principle is to maximize the heat conversion efficiency using plasmonic nanoparticle–light interaction. Due to their unique optical characteristics derived from their anisotropic structure, gold nanostars (GNSs) have gotten significant attention in photothermal therapy. To design a proper cancer treatment, it is vital to study the thermal effect induced close to the gold nanoparticles, in the vicinity, and the cancerous tissue. A temperature-dependent 2D model based on finite element method models is commonly used to simulate near-IR tumor ablation. The bioheat equation describes the photothermal effect within the GNSs and the environment. Surface cooling and heating strategies, such as the periodical heating method and a reduced laser irradiation area, were investigated to address surface overheating problems. We also determined that the optimal laser radius depends on tumor aspect ratio and laser intensity. Our results provide guidelines to evaluate a safe and feasible temperature range, treatment time, optimal laser intensity, and laser radius to annihilate a tumor volume.
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Background Cancer immunotherapy has been gradually introduced and has undergone noteworthy developments in recent years. The number of scientific publications has been expanding, and the progression in this field has been rapidly evolving with time. Objective This study aimed to use bibliometric analysis of the published literature on immunotherapy in cancer to illustrate the research trends over the past 20 years and to summarize the hotspots for future studies. Methods A literature search for medical publications on immunotherapy in cancer from 2000 to 2021 was conducted in the Web of Science Core Collection on March 1, 2022. Visualization analysis was performed using VOSviewer software (version 1.6.16). Results From 2000 to 2021, a total of 18,778 publications were retrieved. Annual publication output grew rapidly from 366 in 2000 to 3,194 in 2021, with a clear increase in publications in 2017. The USA issued the largest number of publications (n = 6,739, 35.89%), with the University of Texas System making the largest contribution (n = 802, 4.27%). A total of 976 meaningful topics were identified and further classified into 4 different clusters. The most common research topics included ‘expression’, ‘chemotherapy’, ‘dendritic cells’, ‘pembrolizumab’ and ‘open-label’. Highly identified cancer types included hepatocellular, bladder, breast and lung cancer. A shift in popularity from mechanism research to clinical trials was observed, indicating that clinical application would be the center of attention in the future. Conclusions Attention has been given to the field of cancer immunotherapy, and this trend will continue in the future. This study provides an unbiased visualization analysis on this topic in a scale-efficient manner for further research.
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Understanding the mechanism of photoacoustic generation at the nanoscale is key to developing more efficient photoacoustic devices and agents. Unlike the far-field photoacoustic effect that has been well employed in imaging, the near-field profile leads to a complex wave-tissue interaction but is under-studied. Here we show that the spatiotemporal profile of the near-field photoacoustic waves can be shaped by laser pulses, anisotropy, and the spatial arrangement of nanostructure(s). Using a gold nanorod as an example, we discovered that the near-field photoacoustic amplitude in the short axis is ~75% stronger than the long axis, and the anisotropic spatial distribution converges to an isotropic spherical wave at ~50 nm away from the nanorod's surface. We further extend the model to asymmetric gold nanostructures by arranging isotropic nanoparticles anisotropically with broken symmetry to achieve a precisely controlled near-field photoacoustic "focus" largely within an acoustic wavelength.
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Cancer is a dreadful disease and among the prominent causes of death worldwide. The major reasons for the high mortality rate among cancer patients are elevated toxicity, improper oral bioavailability, hydrophobicity, low therapeutic indices, inconsistent circulation, nonspecific biodistribution and inefficiency, and inability to deliver therapeutic agents only to the target sites without inducing adverse effects on healthy tissues and organs. All this has prompted researchers to identify new agents that can treat and/or diagnose cancer efficiently. Apart from this, site-specific drug delivery is an important area of research that is expected to increase the efficacy of the therapeutics and thereby reduce its potential side effects. Recent advances in nanotechnology have opened a new arena in the field of theranostics as well as targeted drug delivery. Considerable work has been done, which has led to the development of non-invasive, efficacious therapeutics and diagnostics modalities as well as a targeted cancer treatment by using nanoscale metallic particles like gold. These gold nanoparticles which are being used in these applications are solid colloidal particles with a 10–100 nm range of size, unique physiochemical and optical properties, a sub-cellular size, and biocompatibility; therefore, they have theranostic potential and could retain and transport a therapeutic agent that is dispersed in a polymer carrier matrix, encapsulated within a polymer shell, covalently attached or adsorbed to the particle surface, or encapsulated within a structure. The review discusses the synthesis, unique properties, and wide spectrum of roles that gold-derived nanoparticles can perform in cancer diagnosis, targeted drug delivery, and therapeutics. Further clinical trials involving gold nanoparticles and the list of technologies that have got patented in cancer treatment and diagnosis have also been discussed.
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Since the angiotensin-converting enzyme 2 (ACE2) protein is abundant on the surface of respiratory cells in the lungs, it has been confirmed to be the entry-point receptor for the spike glycoprotein of SARS-CoV-2. As such, gold nanorods (AuNRs) functionalized with ACE2 ectodomain (ACE2ED) act not only as decoys for these viruses to keep them from binding with the ACE2-expressing cells but also as agents to ablate infectious virions through heat generated from AuNRs under near-infrared (NIR) laser irradiation. Using plasmid containing the SARS-CoV-2 spike protein gene (with a D614G mutation), spike protein pseudotyped viral particles with a lentiviral core and green fluorescent protein reporter were constructed and used for transfecting ACE2-expressing HEK293T cells. Since these viral particles behave like their coronavirus counterparts, they are the ideal surrogates of native virions for studying viral entry into host cells. Our results showed that, once the surrogate pseudoviruses with spike protein encounter ACE2ED-tethered AuNRs, these virions are entrapped, resulting in decreased viral infection to ACE2-expressing HEK293T cells. Moreover, the effect of photothermolysis created by ACE2ED-tagged AuNRs under 808-nm NIR laser irradiation for 5 min led to viral breakdown. In summary, ACE2ED-tethered AuNRs with dual functions (virus decoy and destruction) could have an intriguing advantage in the treatment of diseases involving rapidly mutating viral species such as SARS-CoV-2.
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Today, researchers have proved that peptide-nanoparticles (p-NPs) are effective and potent instruments for the treatment and diagnosis of numerous illnesses, as well as for use in bioimaging applications. In order to create the p-NPs, a variety of bio-conjugation techniques have been used. These applications include many areas such as drug release, targeting and cancer treatment. Peptide-drug conjugates, also known as PDCs, are currently being researched and developed as a potential method for effectively and specifically delivering lethal medications to cancer cells. Peptides have a relatively poor stability in the blood, liver, and kidneys, which is one of the obstacles that must be overcome before they can be effectively used. Furthermore, I demonstrate how the shape, size, density of the peptide, and the protein corona of the peptidegold nanoparticle conjugates (p-AuNPs) impact the biological activity of the conjugates. After that, I will talk about the prospects for clinical translation of p-AuNPs and the difficulties that have been encountered so far. Overall, this research demonstrates that p-AuNPs have the potential to be employed as therapeutic and diagnostic products for the treatment of existence disorders in the future, and that they can be done in an inexpensive manner. Course name: Biotechnology I; Course code: KMU 314
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Background Light-based therapies are promising for treating diseases including cancer, hereditary conditions, and protein-related disorders. However, systems, methods, and devices that deliver light deep inside the body are limited. This study aimed to develop an endovascular therapy-based light illumination technology (ET-BLIT), capable of providing deep light irradiation within the body. Methods The ET-BLIT system consists of a catheter with a single lumen as a guidewire and diffuser, with a transparent section at the distal end for thermocouple head attachment. The optical light diffuser alters the emission direction laterally, according to the optical fibre's nose-shape angle. If necessary, after delivering the catheter to the target position in the vessel, the diffuser is inserted into the catheter and placed in the transparent section in the direction of the target lesion. Findings ET-BLIT was tested in an animal model. The 690-nm near-infrared (NIR) light penetrated the walls of blood vessels to reach the liver and kidneys without causing temperature increase, vessel damage, or blood component alterations. NIR light transmittance from the diffuser to the detector within the organ or vessel was approximately 30% and 65% for the renal and hepatic arteries, respectively. Interpretation ET-BLIT can be potentially used in clinical photo-based medicine, as a far-out technology. ET-BLIT uses a familiar method that can access the whole body, as the basic procedure is comparable to that of endovascular therapy in terms of sequence and technique. Therefore, the use of the ET-BLIT system is promising for many light-based therapies that are currently in the research phase. Funding Supported by Programme for Developing Next-generation Researchers (Japan Science and Technology Agency); JSPS KAKENHI (18K15923, 21K07217); JST-CREST (JPMJCR19H2); JST-FOREST-Souhatsu (JPMJFR2017); The Uehara Memorial Foundation; Yasuda Memorial Medical Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Takeda Science Foundation; The Japan Health Foundation; Takahashi Industrial and Economic Research Foundation; AICHI Health Promotion Foundation; and Princess Takamatsu Cancer Research Fund.
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Goldnanoparticles(AuNPs)havebeenwidelyusedandappliedinscience,biotechnologyandmedicinefields because they have many unique properties including their ease synthesis, optical characteristics and chemical stability. ThepurposeofthepresentstudywasfocusedtoinvestigatetheadvantagesofAuNPsinreductionofestradiolhormone and might employed this phenomenon to treat breast cancer across reducing this hormone and amplification of their effectsacrossirradiationwithx-rays.Atotalnumberofthesubjectsincludedinthisstudywas15womenandallages wererangedbetween18to22yearsold.Theserumderivedfrombloodsamplesofwomenweresub-dividedintotwo groups;thefirstgroupwasservedasacontrolgroupandthesecondgroupwasfirstlymixedwithAuNPsfor24hours and then irradiated with x – rays (5 Gy) .The data obtained from the present study showed a significant decrease (p <0.05) in the concentrations of estradiol hormone of blood samples when mixed with AuNPs compared to non-treated samples ( control group ) and these results recorded a progressive lowering ( p <0.05 ) when the samples –AuNPs mixture irradiated with x- rays ( 5 Gy) in matching with thosenon-treated samples. Moreover, the same results were foundintheactivitiesofcatalaseenzymeanditsresultsconfirmedaremarkablereduction(p<0.05)inbothtreatments (sample- AuNPs and irradiation of this mixture with x-rays. In contrast, levels of malodialdehyde (MDA) were significantly increased (p<0.05) when samples mixed with AuNPs and then they exposed to x-rays as compared to control group. Concerning the correlations among studied parameters were insignificantly different (p>0.05). In conclusion, the AuNPs have ability to reduce estradiol hormone because of generation of free radicals and drop of antioxidantsystemandtheseeffectscanbeamplifiedandpotentiatedthroughexposuretomoderatedoseofx-rays.
Chapter
Metal nanoparticles have been extensively synthesized using physical, chemical, and biological methods due to their exclusive applications, ranging from electronics to pharmaceutics. In pharmaceuticals and biomedical applications, metal nanoparticles such as gold, silver, and copper are widely used in applications such as sensors, imaging, targeted and controlled drug delivery applications. However, the toxicity of nanoparticles plays a critical role in employing them in biomedical applications, as toxic reactions will be a drawback for utilization in biological systems. Therefore in vitro and in vivo toxicity tests using cell and animal models, respectively, play a significant role in analyzing the toxicity of metal nanoparticles. Less toxic metal nanoparticles are highly recommended for targeted and controlled drug delivery applications. This chapter presents an overview of metal nanoparticles, including metal nanocomposites, and their in vitro and in vivo toxic ranges, along with possible synthesis procedures to reduce their toxicity. In addition, the recent metal nanoparticles that have been successfully proved to be useful in drug delivery applications are discussed, along with the future of metal nanoparticles in targeted and controlled delivery of drugs to cure diseases.
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The use of liposomal carriers and the modification of therapeutic molecules through the attachment of poly(ethylene glycol) [PEG] moieties (‘pegylation’) are the most common approaches for enhancing the delivery of parenteral agents. Although ‘classical’ liposomes (i.e. phospholipid bilayer vehicles) have been effective in decreasing the clearance of encapsulated agents and in passively targeting specific tissues, they are associated with considerable limitations. Pegylation may be an effective method of delivering therapeutic proteins and modifying their pharmacokinetic properties, in turn modifying pharmacodynamics, via a mechanism dependent on altered binding properties of the native protein. Pegylation reduces renal clearance and, for some products, results in a more sustained absorption after subcutaneous administration as well as restricted distribution. These pharmacokinetic changes may result in more constant and sustained plasma concentrations, which can lead to increases in clinical effectiveness when the desired effects are concentration-dependent. Maintaining drug concentrations at or near a target concentration for an extended period of time is often clinically advantageous, and is particularly useful in antiviral therapy, since constant antiviral pressure should prevent replication and may thereby suppress the emergence of resistant variants. Additionally, PEG modification may decrease adverse effects caused by the large variations in peak-to-trough plasma drug concentrations associated with frequent administration and by the immunogenicity of unmodified proteins. Pegylated proteins may have reduced immunogenicity because PEG-induced steric hindrance can prevent immune recognition. Two PEG-modified proteins are currently approved by the US Food and Drug Administration; several others, including cytokines such as interferon-α (IFNα), growth factors and free radical scavengers, are under development. Careful assessment of various pegylated IFNα products suggests that pegylated molecules can be differentiated on the basis of their pharmacokinetic properties and related changes in pharmacodynamics. Because the size, geometry and attachment site of the PEG moiety play a crucial role in determining these properties, therapeutically optimised agents must be designed on a protein-by-protein basis.
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Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.
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Gold nanoshells, nanoparticles consisting of a silica core coated with a thin gold shell, exhibit a strong optical resonance that depends sensitively on their core radius and shell thickness. Gold nanoshells have been fabricated with a peak optical extinction that can be varied across the near-infrared region of the spectrum (800 nm–2.2 μm). Multipolar plasmon resonances are clearly resolvable in the extinction spectra and agree well with electromagnetic theory. Additional resonances due to particle aggregation are also observed. The frequency agile infrared properties of these nanoparticles make them particularly attractive for a range of technologically important applications. © 1999 American Institute of Physics.
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Aqueous reduction of hydrogen tetrachloroaurate(III) with alkaline tetrakis(hydroxymethyl) phosphonium chloride yields gold in an ultrafinely divided form as a stable colloidal hydrosol, with mean metal-cluster diameter between 1 and 2 nm, without the need for large organic stabilizing molecules. The ultraviolet-visible extinction spectrum is very similar to those of other gold colloids of similar dimensions and includes a weak plasmon feature. Dispersions with characteristics of yet finer clusters are prepared using lower initial concentrations of Au3+ ions. Boiling the sols in the presence of appropriate colloidal stabilizers (ionic and/or polymeric) is a route to coarser (3-10 nm particle diameter) gold hydrosols.
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BACKGROUND The authors compared the efficacy of percutaneous microwave coagulation therapy (PMCT) and percutaneous ethanol injection therapy (PEIT) in the treatment of patients with cirrhosis and a solitary nodular hepatocellular carcinoma (HCC) ≤ 2 cm in greatest dimension.METHODS Of 43 patients with well-differentiated HCC, 23 were treated with PMCT and 20 with PEIT. Of the 47 patients with moderately or poorly differentiated HCC, 25 were treated with PMCT and 22 with PEIT. In a retrospective, nonrandomized study, the prognoses of 90 patients during the 12–72 months preceding the study were analyzed according to histologic tumor grade.RESULTSThe overall 5-year survival rates for patients with well-differentiated HCC treated with PMCT (70%) and PEIT (78%) were not significantly different. No difference between the patterns of recurrence was observed. Among the patients with moderately or poorly differentiated HCC, overall survival with PMCT (5-year survival rate: 78%) was significantly better than with PEIT (5-year survival rate: 35%) (P = 0.03). Nine of 22 patients with moderately or poorly differentiated HCC treated with PEIT experienced recurrence in the original target subsegment. Only 2 of 25 patients treated with PMCT had a recurrence in the same subsegment as the initial tumor.CONCLUSIONSPMCT may be superior to PEIT for the local control of moderately or poorly differentiated small HCC. Cancer 1999;85:1694–702. © 1999 American Cancer Society.
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Metal nanoshells, consisting of a dielectric core with a metallic shell of nanometer thickness, are a new, composite nanoparticle whose optical resonance can be “designed in” in a controlled manner. By varying the relative dimensions of the core and shell, the optical resonance of these nanoparticles can be varied over hundreds of nanometers in wavelength, across the visible and into the infrared region of the spectrum. We report a general approach to the making of metal nanoshell composite nanoparticles based on molecular self-assembly and colloid reduction chemistry.
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The absorption spectrum of indocyanine green depends on the nature of the solvent medium and on the dye concentration. Binding to plasma proteins causes the principal peaks in the absorption spectrum to shift about 25 nm toward the higher wavelengths. The much greater influence on the spectrum of the dye concentration results from progressive aggregate formation with increasing concentration. Indocyanine green solutions therefore do not follow Lambert-Beer's law above 15 mg-I-1 (in plasma). Indocyanine green solutions in plasma and concentrated (1,000 mg-I-1) solutions in distilled water are stable for at least 4 h. In long-term experiments the optical density of indocyanine green solutions in plasma as well as in distilled water generally diminishes, even in the dark. On the 7th day a new absorption maximum starts to appear at gamma=900 nm, possibly caused by further aggregate formation leading to much larger particles. Spectral stabilization after injection of a concentrated solution into the blood is most rapid when the dye is dissolved in distilled water. Spectral stabilization slows down with decreasing temperature. As rapid spectral stabilization is essential in quantitative dye dilution studies, the practice of adding a albumin and/or isotonic saline solution to the injectate should be discontinued. When a 10 g-1(-1) aqueous solution of indocyanine green is used, spectral stabilization takes less than 1.5 a (at 37 degrees C), which is sufficiently fast for almost any application.
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This study was carried out to investigate the effects of Nd:YAG laser-induced hyperthermia on murine F9 embryonal carcinoma cells in vitro using various power settings, temperatures, and exposure times. F9 cells were plated on gelatin-coated dishes, treated on the following day, and cultured overnight. The following day the killing efficiency of the treatments was estimated by staining the dishes or by labeling the cells with 3H-thymidine. A contact Nd:YAG laser with a frosted-end probe was used. After laser treatments at 39 degrees C, no significant changes were observed in the viability of the cells. Laser treatment at 43 degrees C killed F9 cells, and the effect was related to the power setting used. Using 6 W, the quantity of viable cells progressively decreased after 1-, 2-, and 5-min treatments, and no viable cells were found after a 10-min treatment. Using 10 W, approximately 10% of the cells survived a 1-min laser treatment, but all cells were killed after a 2-min treatment. In the control wells, heated in a water bath for up to 40 min, all cells regularly survived at 43 degrees C. There were much less viable cells in those laser-treated wells where the temperature exceeded 44 degrees C than in those where the temperature was kept at 44 degrees C. In conclusion, the tumoricidic effect of hyperthermia can be potentiated by the use of the contact Nd:YAG laser. At a set temperature the cell killing effect of laser treatment is dependent on the power used and the duration of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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Hyperthermic tumor response induced by 1,064-nm radiation from an Nd:YAG laser was investigated in DBA/2J female mice bearing the SMT-F mammary carcinoma. The measured temperature-depth profiles indicate that hyperthermic temperatures can be achieved in tumors ranging from 3 to 8 mm thick at power inputs on the order of 1 W. For small tumors, a 5-week complete response rate exceeding 50% required 45 minutes at 45.0 degrees C. Control of large tumors (6-8 mm thick) was not achieved. The observed tumor response rates are consistent with semiempirical time-temperature relations based on other heating modalities.
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Due to the wide variability of tissue interactions and the possibility of specific applications, the neodymium-yttrium-aluminum-garnet (Nd:YAG) laser is the most important surgical laser. With the adequate choice of application mode and relationship between interaction time and power density, it can be used for precise cutting in the contact mode with the bare fiber, with either a wide or small coagulation seam. With a handpiece a precise focal coagulation for preparation and hemostatic purposes is possible, as well as cutting with the focussed noncontact beam where additionally a wide coagulation seam is necessary. Endoscopically guided coagulation, vaporization, and cutting are possible with bare fibers which can be introduced through nearly all endoscopes. With increasing importance, the possibility for wide and homogeneous volume coagulation is used to destroy diseased tissues either by noncontact irradiation or interstitial placement of the fiber. Thus, the field of laser application in tumor therapy ranges from the treatment of superficial tumors to endoscopic tumor ablation, resection of neoplastic tissue in parenchymatous organs, and interstitial thermotherapy with coagulation of deep-seated primary and secondary malignancies. With its different application modes the laser can be used as a surgical instrument or as a central therapeutical method, whereby perfect control of tissue interactions is always possible by using either visual control for superficial and endoscopic procedures or magnetic resonance imaging and color-coded duplex sonography as a control for interstitial procedures. During 12 years of clinical work we have developed several application modes and have proved the Nd:YAG laser to be an effective instrument in tumor therapy.
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Some tumor cells express Ags that are potentially recognizable by T lymphocytes and yet do not elicit significant immune responses. To explore new immunotherapeutic strategies aimed at enhancing the recognition of these tumor-associated Ags (TAA), we developed an experimental mouse model consisting of a lethal clone of the BALB/c tumor line CT26 designated CT26.WT, which was transduced with the lacZ gene encoding beta-galactosidase, to create CT26.CL25. The growth rate and lethality of CT26.CL25 and CT26.WT were virtually identical despite the expression by CT26.CL25 of the model tumor Ag in vivo. A recombinant fowlpox virus (rFPV), which is replication incompetent in mammalian cells, was constructed that expressed the model TAA, beta-galactosidase, under the influence of the 40-kDa vaccinia virus early/late promoter. This recombinant, FPV.bg40k, functioned effectively in vivo as an immunogen, eliciting CD8+ T cells that could effectively lyse CT26.CL25 in vitro. FPV.bg40k protected mice from both subcutaneous and intravenous tumor challenge by CT26.CL25, and most surprisingly, mice bearing established 3-day pulmonary metastasis were found to have significant, Ag-specific decreases in tumor burden and prolonged survival after treatment with the rFPV. These observations constitute the first reported use of rFPV in the prevention and treatment of an experimental cancer and suggest that changing the context in which the immune system encounters a TAA can significantly and therapeutically alter the host immune response against cancer.
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Microvascular permeability and interstitial penetration of sterically stabilized liposomes in both normal s.c. tissue and human colon adenocarcinoma LS174T xenograft were quantified by using the dorsal skin-fold chamber implanted in severe combined immunodeficient mice and intravital fluorescence microscopy. Significant extravascular accumulation was the dominant feature of liposome distribution in tumors, whereas only minimal intramural accumulation in postcapillary and collecting venules was observed in normal s.c. tissue. The extravasated liposomes in tumors distributed heterogeneously and formed perivascular clusters that did not move significantly and could be observed for up to 1 week. The effective permeability of tumor vessels to liposomes (2.0 +/- 1.6 x 10(-8) cm/s; n = 23) was six times smaller than that to bovine serum albumin (1.2 +/- 0.5 x 10(-7) cm/s; n = 6). These results provide new insights into the mechanisms of transendothelial pathways of liposomes and improvements in liposome-mediated drug delivery.
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Liposomes containing dioleoyl-N-(monomethoxypoly(ethylene glycol)succinyl)- phosphatidylethanolamine (PEG-PE), and of three characteristic sizes (d > 300 nm, d approximately 150-200 nm, and d < 70 nm), were prepared, injected into mice, and their biodistributions examined following a radioactive lipid phase marker. The large and small liposomes accumulated to elevated levels in spleen and liver, respectively. The intermediate sized liposomes were found to be the longest circulating. Furthermore, when injected into mice bearing murine MC-38 colon carcinoma tumor, an approximate 2-fold increase in the % injected dose per g tumor was observed for the long-circulating liposomes compared to liposomes without PEG-PE. The distribution of the injected liposomes within the tumor was examined by fluorescence microscopy, where the liposomes were labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). The liposomes were found surrounding blood vessels in the tumor, with some degree of extravasation into the tumor mass. A previous explanation for the reduced circulation time of small liposomes has been that they have an ability to pass through the fenestrated liver endothelium and thereby reach the parenchymal cells. DiI-labeled liposomes were therefore used to examine the intrahepatic distribution of the injected liposomes. Liposomes accumulated in liver were localized to Kupffer cells, regardless of liposome size. The small liposomes were not detectable in areas comprised of parenchymal cells when using this fluorescence technique. The reason for reduced long-circulating behavior for the small liposomes may be more directly related to the activity of PEG-PE. Therefore the steric barrier activity of the liposomes was examined by a serum protein binding assay and by streptavidin binding to biotinylated liposomes. The steric barrier was liposome size dependent, with the small liposomes revealing increased protein binding. This decreased steric barrier of the small liposomes may result in increased susceptibility to opsonization and thus explain their more rapid clearance from the circulation. The large liposomes accumulated in spleen were localized in the red pulp and marginal zone. Uptake of the large liposomes may occur by means of a filtration mechanism. These results establish the significance of liposome size in determining liposome circulation time and biodistribution, and are relevant for the optimal design of liposomes for drug delivery.
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Murine mammary tumors were treated using indocyanine green and an 808 nm diode laser, and the in vivo chromophore-enhanced photothermal effects on the tumor burden and on tumor rat survival were investigated. The power of the laser was selected in the range of 5-10 W, and irradiation duration 3-5 min. One percent aqueous indocyanine green solution in a volume of 100-200 microliters was administered in situ, either acutely or 24 h prior to the treatment. The photothermal interaction was apparent under all our treatment conditions with a well-defined spatial containment in this study and the tumor growth was slowed after treatment. The post-treatment observation showed tumor recurrence and metastasis; no long-term survival was achieved with the single application of laser in conjunction with indocyanine green. Our results pose a question on the efficacy of the photothermal interaction even though tumor cell destruction can be achieved in a large and controlled scale. However, this highly selective photothermal impact on the tumor tissue did suggest that this method be applied repeatedly to be more effective and be used as the precursor of other modalities, such as chemotherapy, radiation therapy, immunotherapy, and surgery.
Article
Interstitial Laser Hyperthermia (ILH) has been investigated since the early 80s in the treatment of deep seated tumors. The purpose of this study was to evaluate the efficiency of diode ILH (830 nm) in a subcutaneous tumor model. STUDY DESIGN/MATERIALS AND METHOD: The antitumoral effect of diode ILH was assessed in a randomized study performed on 80 Swiss nu/nu mice. The tumor model was a subcutaneously implanted HT29 colonic carcinoma. The animals were assigned to four groups of 20 mice: Groups 1 and 3 were treated by ILH, groups 2 and 4 were not treated (control groups). Tumors were removed on day 3 in groups 1 and 2, and on day 30 in groups 3 and 4. The treatment was performed on tumors of 8 mm in diameter and a volume of 140 mm3. A laser irradiation of 360 J (power: 0.2 W; irradiation time: 1800 s) was delivered through a 300 microns optical fiber implanted in the tumor. The laser parameters insured temperatures of 46 degrees C in the central part of the tumor and 42 degrees C at the periphery. Tumor features were evaluated on day 3 and day 30. Untreated tumors grew rapidly up to a mean volume of 241 mm3 on day 3 (group 2) and 2,000 mm3 on day 30 (group 4). Treated tumors regressed to a mean volume of 32 mm3 on day 3 (group 1). On day 30, 40% of the tumors had totally disappeared and 60% showed partial response with small and peripheral residual tumor of 172 mm3 on an average, as to say 11.2 times smaller than in group 4. ILH with a low power 830 nm diode laser is an efficient treatment of subcutaneous tumor model. Partial responses are attributed to an insufficient heating at the tumor periphery. More precise control of the peripheral tumor temperature will improve the ILH results.
Article
Photosensitizer-enhanced laser treatment, where dyes are activated in situ by lasers of appropriate wavelengths, provides highly selective tissue destruction, both spatially and temporally, through photophysical reactions. Although laser-sensitizer treatment for cancer can achieve a controlled local tumor cell destruction on a large scale, total tumor eradication may not be accomplished because of the incomplete local tumor killing or the presence of tumor metastases, or both. The long-term control of cancer depends on the host immune surveillance and defense systems in which both cell-mediated and humoral responses are critical. In this study we report a novel minimally invasive cancer treatment combining the laser photophysical effects with the photobiological effects. Irradiation of a rat mammary tumor by an 805 nm diode laser, after an intratumor administration of a specific photosensitizer, indocyanine green in a glycated chitosan gel, caused immediate photothermal destruction of neoplastic cells. Concomitantly this treatment stimulated the immunological defense system against residual and metastatic tumor cells. Increases in survival rate and in the eradication of tumor burden, both primary and metastatic, were observed after this treatment. Furthermore, the resistance of successfully treated rats to tumor rechallenge demonstrated a long-lasting systemic effect of the treatment. These findings indicate that our treatment has triggered a specific humoral immune response in the tumor-bearing rats.
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The authors compared the efficacy of percutaneous microwave coagulation therapy (PMCT) and percutaneous ethanol injection therapy (PEIT) in the treatment of patients with cirrhosis and a solitary nodular hepatocellular carcinoma (HCC) < or = 2 cm in greatest dimension. Of 43 patients with well-differentiated HCC, 23 were treated with PMCT and 20 with PEIT. Of the 47 patients with moderately or poorly differentiated HCC, 25 were treated with PMCT and 22 with PEIT. In a retrospective, nonrandomized study, the prognoses of 90 patients during the 12-72 months preceding the study were analyzed according to histologic tumor grade. The overall 5-year survival rates for patients with well-differentiated HCC treated with PMCT (70%) and PEIT (78%) were not significantly different. No difference between the patterns of recurrence was observed. Among the patients with moderately or poorly differentiated HCC, overall survival with PMCT (5-year survival rate: 78%) was significantly better than with PEIT (5-year survival rate: 35%) (P = 0.03). Nine of 22 patients with moderately or poorly differentiated HCC treated with PEIT experienced recurrence in the original target subsegment. Only 2 of 25 patients treated with PMCT had a recurrence in the same subsegment as the initial tumor. PMCT may be superior to PEIT for the local control of moderately or poorly differentiated small HCC.
Article
We have examined the size dependence of extravasation and interstitial localization of polyethyleneglycol-coated liposomes (PEG-liposomes) in the solid tumor tissue by means of electron microscopic observation. Liposomes composed of distearoyl phosphatidylcholine, cholesterol and distearoylphosphatidylethanolamine derivative of polyethyleneglycol (PEG) were prepared in various size ranges. PEG-liposomes with an average diameter of 100-200 nm showed the most prolonged circulation time and the greatest tumor accumulation in all the solid tumors employed in this experiment. Although large PEG-liposomes with a diameter of 400 nm showed a short circulation time in normal mice, the results in splenectomized mice indicated that they do have an intrinsic prolonged circulation character in vivo. However, large PEG-liposomes could not extravasate into solid tumor tissue. These results indicate that the size of liposomes is critical for extravasation. The electron microscopic observations revealed the almost exclusive engulfment of extravasated liposomes by tumor-associated macrophages; very few were taken up by tumor cells.
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Tumor ablation by using radio-frequency energy has begun to receive increased attention as an effective minimally invasive approach for the treatment of patients with a variety of primary and secondary malignant neoplasms. To date, these techniques have been used to treat tumors located in the brain, musculoskeletal system, thyroid and parathyroid glands, pancreas, kidney, lung, and breast; however, liver tumor ablation has received the greatest attention and has been the subject of a large number of published reports. In this article, the authors review the technical developments and early laboratory results obtained with radio-frequency ablation techniques, describe some of the early clinical applications of these techniques, and conclude with a discussion of challenges and opportunities for the future.
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Progress continues in the development of smaller, more penetrable probes for biological imaging.
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Radiofrequency ablation of solid tumors is produced by frictional heating caused when ions in the tissue attempt to follow the changing directions of a high-frequency alternating current. The radiofrequency probe is typically placed under ultrasound guidance, and the ablation is performed with real-time ultrasound monitoring. Radiofrequency ablation has been demonstrated to be effective in the treatment of unresectable hepatic tumors, and promising results have also been obtained in tumors of the lung, bone, brain, kidney, prostate gland, and pancreas. Most recently, radiofrequency ablation has been tested in the treatment of invasive breast tumors. A preliminary study reported that intraoperative radiofrequency ablation causes invasive breast cancer cell death in patients with locally advanced breast cancer. An ongoing study is investigating the use of radiofrequency ablation for the treatment of breast tumors 2 cm or less in diameter.
Article
Enhanced vascular permeability of tumor and angiogenesis both sustain tumor growth mediated by many vascular mediators and high vascular density. Impaired reticuloendothelial/lymphatic clearance of macromolecules from the tumor, or lack of such clearance, is another unique characteristic of tumor tissue (Fig. 9). The enhanced permeability and retention (EPR) effect is the basis for the selective targeting of macromolecular drugs to tumor, and the EPR concept is now utilized for selective delivery of macromolecular anticancer agents, which is not possible for low-molecular-weight drugs because of rapid washout by capillary blood flow. This EPR concept has been validated in clinical settings with hepatoma and other solid tumors (7, 12, 49-52, 54, 56). More recently, HPMA-copolymer conjugated PK-1 has also demonstrated this effect (12, 34, 57). More efficient drug delivery to tumor, especially of macromolecular drugs, may be possible by enhancing the EPR effect with the use of various vascular permeability mediators or potentiators. Suppression of the EPR effect by the use of appropriate inhibitors or antidotes, such as the bradykinin antagonist HOE 140 and protease inhibitors or NOS inhibitors, may also be possible. Thus, one may be able to suppress or retard tumor growth and tumor metastasis. Also, by suppressing vascular permeability with antidotes such as the bradykinin antagonist HOE 140, pleural fluid in lung cancer and ascitic fluid in abdominal carcinomatosis may be controlled and the clinical course of cancer patients may be improved. Arterial infusion of Lipiodol will be by far the best targeting method, in that a tumor/blood ratio of >2000 can be achieved, which is considerably better than that obtained with monoclonal antibody (which is actually not much better than that seen with intravenously injected polymeric drugs in general). In summary, tumor vasculature can be an excellent target for delivery of macromolecular anticancer drugs, the most beneficial class of drugs in view of tumor-selective targeting based on the EPR effect in solid tumor (7, 8, 12, 36, 49-53, 55-58).
Article
The powerful union of focused ultrasound and magnetic resonance imaging (MRI) has created a new approach to noninvasive surgery. By using this integrated therapy delivery system, the physician can correctly localize tumors, optimally target acoustic energy, monitor energy deposition in real time, and accurately control the deposited thermal dose within the entire tumor volume. This satisfies the requirements for "ideal surgery." In a real sense, MRI provides the "road map" by which focused ultrasound surgery (FUS) is followed. The advantages of MRI over ultrasound guidance in controlling FUS lie in the more sensitive detection of tumor target, the real-time detection of tissue temperature, and the confirmation of thermally induced tissue changes-powerful features that eventually can replace the traditional surgical approach. Applying software that connects the therapy and imaging system (the "Dosimetry Workstation"), the physician can generate an entire treatment plan from quantifying temperature changes to positioning the therapy transducer. The noninvasive debulking of tumors without disturbing adjacent, functionally intact structures is thereby accomplished.
Article
Most solid tumors are known to exhibit highly enhanced vascular permeability, similar to or more than the inflammatory tissues. Common denominators affecting both cancer and inflammatory lesions are now well known: bradykinin (BK), nitric oxide (NO), peroxynitrite (ONOO(-)), prostaglandins (PGs), collagenases or matrix metalloproteinases (MMPs) and others. Incidentally, enzymes involved in these mediator syntheses are upregulated or activated. Initially described vascular permeability factor (VPF) (proteinaceous) was later identified to be the same as vascular endothelial growth factor (VEGF), which promotes angiogenesis of cancer tissues as well. These mediators cross-talk or co-upregulate each other, such as BK-NO-PGs system. Therefore, vascular permeability observed in solid tumor may reflect the other side of the coin (angiogenesis). The vascular permeability and accumulation of plasma components in the interstitium described here is applicable for predominantly macromolecules (molecular weight, Mw>45 kDa), but not for low molecular compounds as most anticancer agents are. Macromolecular compounds (e.g., albumin, transferrin) or many biocompatible water-soluble polymers show this effect. Furthermore, they are not cleared rapidly from the sites of lesion (cancer/inflammatory tissue), thus, remain for prolonged time, usually for more than a few days. This phenomenon of "enhanced permeability and retention effect" observed in cancer tissue for macromolecules and lipids is coined "EPR effect", which is now widely accepted as a gold standard for anticancer drug designing to seek more cancer-selective targeting using macromolecular drugs. Consequently, drastic reduction of the systemic side effect is observed, while the macromolecular drugs will continuously exert antitumor activity. Other advantages of macromolecular drugs are also discussed.
Article
A rapid immunoassay capable of detecting analyte within complex biological media without any sample preparation is described. This was accomplished using gold nanoshells, layered dielectric-metal nanoparticles whose optical resonance is a function of the relative size of its constituent layers. Aggregation of antibody/nanoshell conjugates with extinction spectra in the near-infrared was monitored spectroscopically in the presence of analyte. Successful detection of immunoglobulins was achieved in saline, serum, and whole blood. This system constitutes a simple immunoassay capable of detecting sub-nanogram-per-milliliter quantities of various analytes in different media within 10-30 min.
Sizedependent extravasation and interstitial localization of polyethyleneglycol liposomes in solid tumor-bearing mice Effect of liposome size on the circulation time and intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes
  • O Ishida
  • K Maruyama
  • K Sasaki
  • M Iwatsuru
  • D C Litzinger
  • A M Buiting
  • N Rooijen
  • L Huang
O. Ishida, K. Maruyama, K. Sasaki, M. Iwatsuru, Sizedependent extravasation and interstitial localization of polyethyleneglycol liposomes in solid tumor-bearing mice, Int. J. Pharm. 190 (1999) 49–56. [20] D.C. Litzinger, A.M. Buiting, N. van Rooijen, L. Huang, Effect of liposome size on the circulation time and intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes, Biochim. Biophys. Acta 1190 (1994) 99 –107.
Guide for the Care and Use of Laboratory Animals
National Research Council, Guide for the Care and Use of Laboratory Animals, National Academy Press, Washington, DC, 1996.