No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Engineering Magnetic Nanoclusters for Highly Efficient Heating in Radio-Frequency Nanowarming
... La síntesis solvotermal se sirve de altas temperaturas y presiones (por encima del punto de ebullición del disolvente) para aumentar la tasa de interacción de los reactivos. Los solventes son variados, empleándose el keroseno [6] y el etilenglicol (EG), este último sirviéndose de iones de Ni 2+ como agente competidor con los iones de Fe 2+ para controlar el tamaño de las NPM de óxido de hierro [12]. ...
... En segundo lugar, las NPM generalmente no son eléctricamente neutras, por lo que deben estabilizarse añadiendo un revestimiento como puede ser el ácido cítrico [10], el polietilenglicol (PEG) [5], [8], [15], las resinas [12] o el trimetoxilsilano (TMS) [13]. En estudios de nanowarming de corazón de ratón [18] el recubrimiento con PEG es precedido de una fina capa de ácido oleico. ...
... La pureza y composición de las nanopartículas se verifican mediante difracción de rayos X (DRX) y la Espectroscopía de Emisión Atómica con Plasma de Acoplamiento Inductivo (EEA-PAI) [12]. ...
MoleQla (ISSN: 2173-0903): Las nanopartículas magnéticas (NPM) de hierro han alcanzado un alto interés en la criopreservación. La necesidad de un calentamiento penetrante, rápido, escalable y homogéneo de las muestras criopreservadas ha llevado al uso de NPM mediante el nanocalentamiento (nanowarming) empleando campos electromagnéticos. En general, las NPM se revisten de óxidos, polímeros o resinas para estabilizar las NPM, mejorar la distribución coloidal y la biocompatibilidad. En este trabajo se presentan casos de uso en el nanowarming aplicado a tejidos biológicos, detallando los métodos de síntesis, caracterización y empleo, junto con sus particularidades. Posteriormente, se aborda la cuestión de la biocompatibilidad y se enumeran un conjunto de buenas prácticas para el empleo eficiente de NPM en criopreservación.
Palabras Claves-Nanopartículas magnéticas, nanocalentamiento, nanowarming, criopreservación, biocompatibilidad.
... 101 Several studies have demonstrated that the colloidal and thermal stability of MNPs in VS55 can be maintained though surface coating with resorcinol-formaldehyde resin or silica. [104][105][106][107] Additionally, surface modification with poly(ethylene glycol) has been shown to reduce cellular interactions and thus cytotoxicity. 106,107 Manuchehrabadi achieved nanowarming of porcine arteries and porcine aortic heart valve leaflet tissues using magnetic heating. ...
Magnetic nanoparticles (MNPs) are highly versatile nanomaterials in nanomedicine, owing to their diverse magnetic properties, which can be tailored through variations in size, shape, composition, and exposure to inductive magnetic...
Radiofrequency (RF) heating is a new, less invasive alternative to invasive heating methods that use nanoparticles for tumour therapy. But pinpoint local heating is still hard. Molecular interactions form a hybrid structure with unique electrical characteristics that enable RF heating in this work, which explores RF heating in a biological cell (yeast)‐2D FeS2 system. Substantial processes have been uncovered via experimental investigations and density functional theory (DFT) computations. At 3 W and 50 MHz, RF heating reaches 54°C in 40 s, which is enough to kill yeast cells, while current‐voltage measurements reveal ionic diode‐like properties. Interactions between yeast lipid molecules and 2D FeSk, as shown by density‐functional theory calculations, cause an imbalance in the distribution of charges and the creation of polar, conductive channels. Insights into biological heating applications based on radio frequency (RF) technology are offered by this work, which lays forth a framework for investigating 2D material‐biomolecule interactions.
Fe3O4@SiO2/4A magnetic nanocomposites (magnetic 4A zeolite) have been synthesized by hydrothermal method which endowed 4A zeolite with magnetic separation characteristics. XRD results showed that the magnetic 4A zeolite had the characteristic diffraction peaks of both 4A zeolite and Fe3O4. The SEM images displayed the combination of 4A zeolite and Fe3O4. N2 physical adsorption showed that magnetic 4A zeolite had a large specific surface area and can provide a large number of adsorption sites for ammonia nitrogen. The magnetic separation results showed that magnetic 4A zeolite exhibited fast response to external magnetic field, and the saturation strength measured by VSM was 5.85 emu g−1, indicating the superparamagnetic properties of magnetic 4A zeolite. The removal rate of ammonia nitrogen by FSA-M-1 sample reached to 43.18%. After 6 rounds of repeated adsorption experiments, each sample’s magnetic recovery rate was above 95%, and the removal rate of ammonia nitrogen was higher than 36%.
A sol–gel technique was used to synthesize MZnFe2O4 (M = Ni, Mg, Mn) spinel ferrite composites. The post-synthesis sintering of the nanocomposites was done at 700 °C for 5 h, followed by non-thermal microwave plasma treatment for 60 min. X-ray diffraction (XRD) analysis of the nanocomposites was conducted to comprehend the cation distribution of pristine and plasma-modified nanocomposites. XRD intensity of peaks for (220), (311), (400) and (440) planes were used to determine the cations distribution using intensity ratio method. The plasma-modified nanocomposites showed a decrease in the intensity ratio of XRD peaks and an increase in the size of the crystallites. The plasma-modified ZnNiFeO4 showed a photocatalytic activity of 95% against RhB dye, ZnMgFe2O4 showed photocatalytic activity of 87%, and ZnMnFe2O4 showed a photocatalytic activity of 90%. The key drivers of high dye degradation efficiency are surface functionalization, removal of oxides and reduced band gap of the plasma-modified nanocomposites.
The wide accessibility to nanostructures with high uniformity and controllable sizes and morphologies provides great opportunities for creating complex superstructures with unique functionalities. Employing anisotropic nanostructures as the building blocks significantly enriches the superstructural phases, while their orientational control for obtaining long-range orders has remained a significant challenge. One solution is to introduce magnetic components into the anisotropic nanostructures to enable precise control of their orientations and positions in the superstructures by manipulating magnetic interactions. Recognizing the importance of magnetic anisotropy in colloidal assembly, we provide here an overview of magnetic field-guided self-assembly of magnetic nanoparticles with typical anisotropic shapes, including rods, cubes, plates, and peanuts. The Review starts with discussing the magnetic energy of nanoparticles, appreciating the vital roles of magneto-crystalline and shape anisotropies in determining the easy magnetization direction of the anisotropic nanostructures. It then introduces superstructures assembled from various magnetic building blocks and summarizes their unique properties and intriguing applications. It concludes with a discussion of remaining challenges and an outlook of future research opportunities that the magnetic assembly strategy may offer for colloidal assembly.
Banking cryopreserved organs could transform transplantation into a planned procedure that more equitably reaches patients regardless of geographical and time constraints. Previous organ cryopreservation attempts have failed primarily due to ice formation, but a promising alternative is vitrification, or the rapid cooling of organs to a stable, ice-free, glass-like state. However, rewarming of vitrified organs can similarly fail due to ice crystallization if rewarming is too slow or cracking from thermal stress if rewarming is not uniform. Here we use “nanowarming,” which employs alternating magnetic fields to heat nanoparticles within the organ vasculature, to achieve both rapid and uniform warming, after which the nanoparticles are removed by perfusion. We show that vitrified kidneys can be cryogenically stored (up to 100 days) and successfully recovered by nanowarming to allow transplantation and restore life-sustaining full renal function in nephrectomized recipients in a male rat model. Scaling this technology may one day enable organ banking for improved transplantation.
Cryopreservation strives to maximize the viability and biofunctionality of cells and tissues by cooling them to a subzero temperature to facilitate storage and delivery. This technology has enabled clinics and labs to preserve rare and crucial samples and is poised to become more important with rising interest in cell therapy. Here, the biological impact of cooling rates on different cellular components is first described, paying special emphasis on the differences between slow cooling and vitrification with a heat transfer perspective based on the Biot number. This is followed by an overview of various classes of chemical‐based cryoprotective agents including small molecules, antifreeze proteins, hydrogels, and cryoprotective nanomaterials. Most importantly, fundamental concepts of cryopreservation including Mazur's “two‐factor hypothesis” are revisited, gaps in them are highlighted, and experiments to validate reported claims to deepen mechanistic understanding of cryoprotection are proposed. A matric is also introduced to assess the suitability of biomaterials for use in cell therapy to support manufacturers in making strategic choices for storing clinical samples. It is believed that this review would inspire readers to scrutinize fundamental concepts in cryopreservation to facilitate the development of new cryoprotective materials and technologies to support the emerging cell manufacturing and therapy industry.
Miniature magnetic-driven robots with multimode motions and high-precision pose sensing capacity (position and orientation) are greatly demanded in in situ manipulation in narrow opaque enclosed spaces. Various magnetic robots have been carried out, whereas their deformations normally remain in single mode, and the lack of the robot’s real-time status leads to its beyond-sight remagnetization and manipulation being impossible. The function integration of pose sensing and multimode motion is still of challenge. Here, a multimotion thin-film robot is created in a novel multilayer structure with a magnetic-driven layer covered by a heating-sensing conductive layer. Such a heating-sensing layer not only can segmentally and on-demand heat the magnetic-driven layer for in situ magnetization reprogramming and multimode motions but also can precisely detect the robot’s pose (position and orientation) from its electrical-resistance effect by creating a small deformation under preset magnetic fields. Under the integration of reprogramming and sensing, necessary multimode motions, i.e., swimming, rolling, crawling, and obstacle-crossing, are achieved under a reprogramming field BRepr of 10 mT, and high-precision poses sensing with an accuracy of ± 3 mm in position and ± 2.5° in orientation is obtained even under a low magnetic strength of BSens of 5 mT, which combined help realize accurate out-of-sight manipulations in the enclosed space environment. Finally, a gastroscope robot for stomach drug delivery has been demonstrated for more gastrointestinal medical treatments.
Preantral follicles are often used as models for cryopreservation and in vitro culture due to their easy availability. As a promising approach for mammalian fertility preservation, vitrification of preantral follicles requires high concentrations of highly toxic penetrating cryoprotective agents (up to 6 M). Here, we accomplish low-concentration-penetrating cryoprotective agent (1.5 M) vitrification of mouse preantral follicles encapsulated in hydrogel by nanowarming. We find that compared with conventional water bath warming, the viability of preantral follicles is increased by 33%. Moreover, the cavity formation rate of preantral follicles after in vitro culture is comparable to the control group without vitrification. Furthermore, the percentage of MII oocytes developed from the vitrified follicles, and the birth rate of offspring following in vitro fertilization and embryo transfer are also similar to the control group. Our results provide a step towards nontoxic vitrification by utilizing the synergistic cryoprotection effect of microencapsulation and nanowarming.
Cryopreservation by vitrification has far-reaching implications. However, rewarming techniques that are rapid and scalable (both in throughput and biosystem size) for low concentrations of cryoprotective agent (CPA) for reduced toxicity are lacking, limiting the potential for translation. Here, we introduce a joule heating–based platform technology, whereby biosystems are rapidly rewarmed by contact with an electrical conductor that is fed a voltage pulse. We demonstrate successful cryopreservation of three model biosystems with thicknesses across three orders of magnitude, including adherent cells (~4 µm), Drosophila melanogaster embryos (~50 µm) and rat kidney slices (~1.2 mm) using low CPA concentrations (2–4 M). Using tunable voltage pulse widths from 10 µs to 100 ms, numerical simulation predicts that warming rates from 5 × 10⁴ to 6 × 10⁸ °C/min can be achieved. Altogether, our results present a general solution to the cryopreservation of a broad spectrum of cellular, organismal and tissue-based biosystems.
New preservation technologies may allow for organ banking similar to blood and biomaterial banking approaches.
Pancreatic islet transplantation can cure diabetes but requires accessible, high-quality islets in sufficient quantities. Cryopreservation could solve islet supply chain challenges by enabling quality-controlled banking and pooling of donor islets. Unfortunately, cryopreservation has not succeeded in this objective, as it must simultaneously provide high recovery, viability, function and scalability. Here, we achieve this goal in mouse, porcine, human and human stem cell (SC)-derived beta cell (SC-beta) islets by comprehensive optimization of cryoprotectant agent (CPA) composition, CPA loading and unloading conditions and methods for vitrification and rewarming (VR). Post-VR islet viability, relative to control, was 90.5% for mouse, 92.1% for SC-beta, 87.2% for porcine and 87.4% for human islets, and it remained unchanged for at least 9 months of cryogenic storage. VR islets had normal macroscopic, microscopic, and ultrastructural morphology. Mitochondrial membrane potential and adenosine triphosphate (ATP) levels were slightly reduced, but all other measures of cellular respiration, including oxygen consumption rate (OCR) to produce ATP, were unchanged. VR islets had normal glucose-stimulated insulin secretion (GSIS) function in vitro and in vivo. Porcine and SC-beta islets made insulin in xenotransplant models, and mouse islets tested in a marginal mass syngeneic transplant model cured diabetes in 92% of recipients within 24–48 h after transplant. Excellent glycemic control was seen for 150 days. Finally, our approach processed 2,500 islets with >95% islets recovery at >89% post-thaw viability and can readily be scaled up for higher throughput. These results suggest that cryopreservation can now be used to supply needed islets for improved transplantation outcomes that cure diabetes.
Magnetic nanoparticles, especially superparamagnetic nanoparticles (SPIONs), have attracted tremendous attention for various biomedical applications. Facile synthesis and functionalization together with easy control of the size and shape of SPIONS to customize their unique properties, have made it possible to develop different types of SPIONs tailored for diverse functions/applications. More recently, considerable attention has been paid to the thermal effect of SPIONs for the treatment of diseases like cancer and for nanowarming of cryopreserved/banked cells, tissues, and organs. In this mini-review, recent advances on the magnetic heating effect of SPIONs for magnetothermal therapy and enhancement of cryopreservation of cells, tissues, and organs, are discussed, together with the non-magnetic heating effect (i.e., high Intensity focused ultrasound or HIFU-activated heating) of SPIONs for cancer therapy. Furthermore, challenges facing the use of magnetic nanoparticles in these biomedical applications are presented.
Worldwide, over 26 million patients suffer from heart failure (HF). One strategy aspiring to prevent or even to reverse HF is based on the transplantation of cardiac tissue-engineered (cTE) constructs. These patient-specific constructs aim to closely resemble the native myocardium and, upon implantation on the diseased tissue, support and restore cardiac function, thereby preventing the development of HF. However, cTE constructs off-the-shelf availability in the clinical arena critically depends on the development of efficient preservation methodologies. Short- and long-term preservation of cTE constructs would enable transportation and direct availability. Herein, currently available methods, from normothermic- to hypothermic- to cryopreservation, for the preservation of cardiomyocytes, whole-heart, and regenerative materials are reviewed. A theoretical foundation and recommendations for future research on developing cTE construct specific preservation methods are provided. Current research suggests that vitrification can be a promising procedure to ensure long-term cryopreservation of cTE constructs, despite the need of high doses of cytotoxic cryoprotective agents. Instead, short-term cTE construct preservation can be achieved at normothermic or hypothermic temperatures by administration of protective additives. With further tuning of these promising methods, it is anticipated that cTE construct therapy can be brought one step closer to the patient.
Cryopreservation technology has developed into a fundamental and important supporting method for biomedical applications such as cell‐based therapeutics, tissue engineering, assisted reproduction, and vaccine storage. The formation, growth, and recrystallization of ice crystals are the major limitations in cell/tissue/organ cryopreservation, and cause fatal cryoinjury to cryopreserved biological samples. Flourishing anti‐icing materials and strategies can effectively regulate and suppress ice crystals, thus reducing ice damage and promoting cryopreservation efficiency. This review first describes the basic ice cryodamage mechanisms in the cryopreservation process. The recent development of chemical ice‐inhibition molecules, including cryoprotectant, antifreeze protein, synthetic polymer, nanomaterial, and hydrogel, and their applications in cryopreservation are summarized. The advanced engineering strategies, including trehalose delivery, cell encapsulation, and bioinspired structure design for ice inhibition, are further discussed. Furthermore, external physical field technologies used for inhibiting ice crystals in both the cooling and thawing processes are systematically reviewed. Finally, the current challenges and future perspectives in the field of ice inhibition for high‐efficiency cryopreservation are proposed.
Background
Magnetic fluid heating has great potential in the fields of thermal medicine and cryopreservation. However, variations among experimental parameters, analysis methods and experimental uncertainty make quantitative comparisons of results among laboratories difficult. Herein, we focus on the impact of calculating the specific absorption rate (SAR) using Time-Rise and Box-Lucas fitting. Time-Rise assumes adiabatic conditions, which is experimentally unachievable, but can be reasonably assumed (quasi-adiabatic) only for specific and limited evaluation times when heat loss is negligible compared to measured heating rate. Box-Lucas, on the other hand, accounts for heat losses but requires longer heating.
Methods
Through retrospective analysis of data obtained from two laboratories, we demonstrate measurement time is a critical parameter to consider when calculating SAR. Volumetric SAR were calculated using the two methods and compared across multiple iron-oxide nanoparticles.
Results
We observed the lowest volumetric SAR variation from both fitting methods between 1–10 W/mL, indicating an ideal SAR range for heating measurements. Furthermore, our analysis demonstrates that poorly chosen fitting method can generate reproducible but inaccurate SAR.
Conclusion
We provide recommendations to select measurement time for data analysis with either Modified Time-Rise or Box-Lucas method, and suggestions to enhance experimental precision and accuracy when conducting heating experiments.
Nanowarming of cryopreserved organs perfused with magnetic cryopreservation agents (mCPAs) could increase donor organ utilization by extending preservation time and avoiding damage caused by slow and nonuniform rewarming. Here, we report formulation of an mCPA containing superparamagnetic iron oxide nanoparticles (SPIONs) that are stable against aggregation in the cryopreservation agent VS55 before and after vitrification and nanowarming and that achieve high-temperature rise rates of up to 321°C/min under an alternating magnetic field. These SPIONs and mCPAs have low cytotoxicity against primary cardiomyocytes. We demonstrate successful perfusion of whole rat hearts with the mCPA and removal using Custodiol HTK solution, even after vitrification, cryostorage in liquid nitrogen for 1 week, and nanowarming under an alternating magnetic field. Quantification of SPIONs in the hearts using magnetic particle imaging demonstrates that the formulated mCPAs are suitable for perfusion, vitrification, and nanowarming of whole organs with minimal residual iron in tissues.
Photothermal actuators have attracted increasing attention due to their ability to convert light energy into mechanical deformation and locomotion. This work reports a freestanding, multidirectional photothermal robot that can walk along a predesigned pathway by modulating laser polarization and on–off switching. Magnetic–plasmonic hybrid Fe3O4/Ag nanorods are synthesized using an unconventional templating approach. The coupled magnetic and plasmonic anisotropy allows control of the rod orientation, plasmonic excitation, and photothermal conversion by simply applying a magnetic field. Once the rods are fixed with desirable orientations in a bimorph actuator by magnetic‐field‐assisted lithography, the bending of the actuator can be controlled by switching the laser polarization. A bipedal robot is created by coupling the rod orientation with the alternating actuation of its two legs. Irradiating the robot by a laser with alternating or fixed polarization synergistically results in basic movement (backward and forward) and turning (including left‐, right‐, and U‐turn), respectively. A complex walk along predesigned pathways can be potentially programmed by combining the movement and turning modes of the robots. This strategy provides an alternative driving mechanism for preparing functional soft robots, thus breaking through the limitations in the existing systems in terms of light sources and actuation manners.
Cryopreserved tissues are increasingly needed in biomedical applications. However, successful cryopreservation is generally only reported for thin tissues (≤1 mm). This work presents several innovations to reduce cryoprotectant (CPA) toxicity and improve tissue cryopreservation, including 1) improved tissue warming rates through radiofrequency metal form and field optimization and 2) an experimentally verified predictive model to optimize CPA loading and rewarming to reduce toxicity. CPA loading is studied by microcomputed tomography (µCT) imaging, rewarming by thermal measurements, and modeling, and viability is measured after loading and/or cryopreservation by alamarBlue and histology. Loading conditions for three common CPA cocktails (6, 8.4, and 9.3 m) are designed, and then fast cooling and metal forms rewarming (up to 2000 °C min⁻¹) achieve ≥90% viability in cryopreserved 1–2 mm arteries with various CPAs. Despite high viability by alamarBlue, histology shows subtle changes after cryopreservation suggesting some degree of cell damage especially in the central portions of thicker arteries up to 2 mm. While further studies are needed, these results show careful CPA loading and higher metal forms warming rates can help reduce CPA loading toxicity and improve outcomes from cryopreservation in tissues while also offering new protocols to preserve larger tissues ≥1 mm in thickness.
We report here that dissolution and regrowth of resorcinol formaldehyde (RF) colloidal particles can occur spontaneously when they are subjected to etching in solvents such as ethanol and tetrahydrofuran, resulting in the formation of hollow nanostructures with controllable shell thickness. The hollowing process of the RF particles is attributed to their structural inhomogeneity, which is resulting from the successive deposition of oligomers with different chain lengths during their initial growth. As the near-surface layer of RF colloids mainly consists of long-chain oligomers while the inner part of short-chain oligomers, selective etching removes the latter and produces the hollow structures. By revealing the important effects of the condensation degree of RF, the etching time and temperature, and the composition of solvents, we demonstrate that the morphology and structure of the resulting RF nanostructures can be conveniently and precisely controlled. This study not only improves our understanding of the structural heterogeneity of colloidal polymer particles, but also provides a practical and universal self-templated approach for the synthesis of hollow nanostructures.
Cryopreservation technology allows long‐term banking of biological systems. However, a major challenge to cryopreserving organs remains in the rewarming of large volumes (>3 mL), where mechanical stress and ice formation during convective warming cause severe damage. Nanowarming technology presents a promising solution to rewarm organs rapidly and uniformly via inductive heating of magnetic nanoparticles (IONPs) preloaded by perfusion into the organ vasculature. This use requires the IONPs to be produced at scale, heat quickly, be nontoxic, remain stable in cryoprotective agents (CPAs), and be washed out easily after nanowarming. Nanowarming of cells and blood vessels using a mesoporous silica‐coated iron oxide nanoparticle (msIONP) in VS55, a common CPA, has been previously demonstrated. However, production of msIONPs is a lengthy, multistep process and provides only mg Fe per batch. Here, a new microporous silica‐coated iron oxide nanoparticle (sIONP) that can be produced in as little as 1 d while scaling up to 1.4 g Fe per batch is presented. sIONP high heating, biocompatibility, and stability in VS55 is also verified, and the ability to perfusion load and washout sIONPs from a rat kidney as evidenced by advanced imaging and ICP‐OES is demonstrated. Nanowarming is a new technology that could solve the technical challenge of volumetric rewarming of cryopreserved biological samples. With the aim of scaling up nanowarming technology from cell and simple tissues to a whole organ, a scalable silica‐coated iron oxide nanoparticle is synthesized and tested for cell nanowarming and organ perfusional loading and removal.
Ferromagnetic Co35Fe65, Fe, Co, and Ni nanowires have high saturation magnetizations (Ms) and magnetic anisotropies, making them ideal for magnetic heating in an alternating magnetic field (AMF). Here, Au-tipped nanowires were coated with polyethylene glycol (PEG) and specific absorption rates (SAR) were measured in glycerol. SAR increased when using metals with increasing Ms (Co35Fe65 > Fe > Co > Ni), reaching 1610 ± 20 W g-1 metal at 1 mg metal per ml glycerol for Co35Fe65 nanowires using 190 kHz and 20 kA m-1. Aligning these nanowires parallel to the AMF increased SAR up to 2010 W g-1 Co35Fe65. Next, Co35Fe65 nanowires were used to nanowarm vitrified VS55, a common cryoprotective agent (CPA).Nanowarming rates up to 1000 °C min-1 (5 mg Co35Fe65 per ml VS55) were achieved, which is 20× faster than the critical warming rate (50 °C min-1) for VS55 and other common CPAs. Human dermal fibroblast cells exposed to VS55, and Co35Fe65 nanowire concentrations of 0, 1 and 2.5 mg Fe per ml all showed similar cell viability, indicating that the nanowires had minimal cytotoxicity. With the ability to provide rapid and uniform heating, ferromagnetic nanowires have excellent potential for nanowarming cryopreserved tissues.
Injectable stem cell‐hydrogel constructs hold great potential for regenerative medicine and cell‐based therapies. However, their clinical application is still challenging due to their short shelf‐life at ambient temperature and the time‐consuming fabrication procedure. Banking the constructs at cryogenic temperature may offer the possibility for their “off‐the‐shelf” availability to end‐users. However, ice formation during the cryopreservation process may compromise the construct quality and cell viability. Vitrification, cooling biological samples without apparent ice formation, has been explored to resolve the challenge. However, contemporary vitrification methods are limited to very small volume (up to ≈0.25 mL) and/or need highly toxic and high concentration (up to ≈8 m) of permeable cryoprotectants (pCPAs). Here, it is shown that polytetrafluoroethylene (PTFE, best known as Teflon for making nonstick cookware) capillary is flexible and unusually stable at cryogenic temperatures. By using the PTFE capillary as a flexible cryopreservation vessel together with alginate hydrogel microencapsulation and Fe3O4 nanoparticle‐mediated nanowarming to suppress ice formation, massive‐volume (e.g., 10 mL) vitrification of cell‐alginate hydrogel constructs with low concentrations (≈2.5 m) of pCPAs can be achieved. This may greatly facilitate the use of stem cell‐based constructs for tissue regeneration and cell based therapies in the clinic.
Magnetic nanoparticles mediated hyperthermia is a very promising therapy for cancer treatment. In this field, superparamagnetic iron oxide nanoparticles (SPIONs) have been commonly employed due to their intrinsic biocompatibility, but they present some limitations that restrict their heating efficiency (SAR). Therefore, we have investigated how tuning the size and shape of these iron oxide nanoparticles can be useful to enhance their hyperthermia results. Monodisperse and highly crystalline iron oxide nanoparticles have been synthesized by thermal decomposition in two different shapes (spheres and cubes) in a wide range of sizes, ~10-100 nm. We have thoroughly characterized them both structurally (XRD, TEM) and magnetically (PPMS), and then we have analyzed their heating efficiency using a combination of calorimetric and AC magnetometry measurements (0-800 Oe, 300 kHz). We have been able to delimit a range of optimum sizes to maximize the heating efficiency of these nanoparticles depending on their shape. We find that the nanospheres tend to heat better for sizes around 30-50 nm, while the nanocubes show a sharp increase in the heating efficiency around 30-35 nm. The SAR variation has been related to the effective anisotropy of the nanoparticles that depends on the effect of arrangement and dipolar interactions.
Significant progress has recently been made in the synthesis of Fe3O4@C nanospheres with uniform, monodisperse and tunable carbon shells. Fe3O4@C nanospheres were obtained by directly carbonizing Fe3O4@polymer which was synthesized by a versatile and economical Stöber method with resorcinol and formaldehyde as precursors. The synthesis conditions in the formation of Fe3O4@polymer were systematically investigated. It was found that the yield of the Fe3O4@polymer is highly influenced by the concentration of ammonium hydroxide, and the monodispersity is mainly affected by the concentration of ammonium hydroxide and the citrate group sites outside the surfaces of the Fe3O4 nanospheres. Interestingly, carbonization of Fe3O4@polymer at high temperature makes the grain sizes of Fe3O4 in Fe3O4@C samples larger than those in the Fe3O4 sample, which makes the saturation magnetization value for the Fe3O4@C samples higher than those of common obtained materials. The adsorption performance of Fe3O4@C for anthracene was tested both in water and in cyclohexane solution; it shows fast adsorption rates (about 1 h to reach equilibrium in water and 3 h in cyclohexane solution) and high adsorption capacities (31.5 mg g−1 in water and 2 mg g−1 in cyclohexane solution), which are ascribed to its high uniformity and monodispersity. These make Fe3O4@C an ideal adsorption and enrichment material, especially for polycyclic aromatic hydrocarbons in water and in organic solvents.
In a ground-breaking development, rat kidneys have been cryopreserved for an unprecedented duration of 100 days and subsequently transplanted successfully after nano-rewarming. This extraordinary achievement opens new possibilities for the field of organ banking.
For full-text access: https://rdcu.be/dhYJl
Rapid and uniform rewarming is critical to cryopreservation. Current rapid rewarming methods require complex physical field application devices (such as lasers or radio frequencies) and the addition of nanoparticles as heating media. These complex devices and nanoparticles limit the promotion of the rapid rewarming method and pose potential biosafety concerns. In this work, a joule heating-based rapid electric heating chip (EHC) was designed for cryopreservation. Uniform and rapid rewarming of biological samples in different volumes can be achieved through simple operations. EHC loaded with 0.28 mL of CPA solution can achieve a rewarming rate of 3.2 × 105 °C/min (2.8 mL with 2.3 × 103 °C/min), approximately 2 orders of magnitude greater than the rewarming rates observed with an equal capacity straw when combined with laser nanowarming or magnetic induction heating. In addition, the degree of supercooling can be significantly reduced without manual nucleation during the cooling of the EHC. Subsequently, the results of cryopreservation validation of cells and spheroids showed that the cell viability and spheroid structural integrity were significantly improved after cryopreservation. The viability of human lung adenocarcinoma (A549) cells postcryopreservation was 97.2%, which was significantly higher than 93% in the cryogenic vials (CV) group. Similar results were seen in human mesenchymal stem cells (MSCs), with 93.18% cell survival in the EHC group, significantly higher than 86.83% in the CV group, and cells in the EHC group were also significantly better than those in the CV group for further apoptosis and necrosis assays. This work provides an efficient rewarming protocol for the cryopreservation of biological samples, significantly improving the quantity and quality of cells and spheroids postcryopreservation.
Regenerative medicine has the potential to revolutionize healthcare by providing transplant options for patients suffering from tissue disease or organ failure. Cryopreservation offers a promising solution for long-term tissue and...
Magnetic nanoparticles are increasingly used in medical applications, including cancer treatment by magnetic hyperthermia. This protocol describes a solvothermal-based process to prepare, at the gram scale, ferrite nanoparticles with well-defined shape, i.e., nanocubes, nanostars and other faceted nanoparticles, and with fine control of structural/magnetic properties to achieve point-of-reference magnetic hyperthermia performance. This straightforward method comprises simple steps: (i) making a homogeneous alcoholic solution of a surfactant and an alkyl amine; (ii) adding an organometallic metal precursor together with an aldehyde molecule, which acts as the key shape directing agent; and (iii) reacting the mixture in an autoclave for solvothermal crystallization. The shape of the ferrite nanoparticles can be controlled by the structure of the aldehyde ligand. Benzaldehyde and its aromatic derivatives favor the formation of cubic ferrite nanoparticles while aliphatic aldehydes result in spherical nanoparticles. The replacement of the primary amine, used in the nanocubes synthesis, with a secondary/tertiary amine results in nanoparticles with star-like shape. The well-defined control in terms of shape, narrow size distribution (below 5%), compositional tuning and crystallinity guarantees the preparation, at the gram scale, of nanocubes/star-like nanoparticles that possess, under magnetic field conditions of clinical use, specific adsorption rates comparable to or even superior to those obtained through thermal decomposition methods, which are typically prepared at the milligram scale. Here, gram-scale nanoparticle products with benchmark features for magnetic hyperthermia applications can be prepared in ~10 h with an average level of expertise in chemistry.
Liver cryopreservation has the potential to enable indefinite organ banking. This study investigated vitrification—the ice-free cryopreservation of livers in a glass-like state—as a promising alternative to conventional cryopreservation, which uniformly fails due to damage from ice formation or cracking. Our unique “nanowarming” technology, which involves perfusing biospecimens with cryoprotective agents (CPAs) and silica-coated iron oxide nanoparticles (sIONPs) and then, after vitrification, exciting the nanoparticles via radiofrequency waves, enables rewarming of vitrified specimens fast enough to avoid ice formation and uniformly enough to prevent cracking from thermal stresses, thereby addressing the two main failures of conventional cryopreservation. This study demonstrates the ability to load rat livers with both CPA and sIONPs by vascular perfusion, cool them rapidly to an ice-free vitrified state, and rapidly and homogenously rewarm them. While there was some elevation of liver enzymes (Alanine Aminotransferase) and impaired indocyanine green (ICG) excretion, the nanowarmed livers were viable, maintained normal tissue architecture, had preserved vascular endothelium, and demonstrated hepatocyte and organ-level function, including production of bile and hepatocyte uptake of ICG during normothermic reperfusion. These findings suggest that cryopreservation of whole livers via vitrification and nanowarming has the potential to achieve organ banking for transplant and other biomedical applications.
Cryopreservation of cells and biologics underpins all biomedical research from routine sample storage to emerging cell-based therapies, as well as ensuring cell banks provide authenticated, stable and consistent cell products. This field began with the discovery and wide adoption of glycerol and dimethyl sulfoxide as cryoprotectants over 60 years ago, but these tools do not work for all cells and are not ideal for all workflows. In this Review, we highlight and critically review the approaches to discover, and apply, new chemical tools for cryopreservation. We summarize the key (and complex) damage pathways during cellular cryopreservation and how each can be addressed. Bio-inspired approaches, such as those based on extremophiles, are also discussed. We describe both small-molecule-based and macromolecular-based strategies, including ice binders, ice nucleators, ice nucleation inhibitors and emerging materials whose exact mechanism has yet to be understood. Finally, looking towards the future of the field, the application of bottom-up molecular modelling, library-based discovery approaches and materials science tools, which are set to transform cryopreservation strategies, are also included. Cryopreservation is a platform technology that underpins the delivery of complex therapies to patients and enables fundamental cell biology by allowing the banking and recovery of viable cells. This Review summarizes the role, and opportunities, for chemistry-driven approaches to cryopreservation, beyond formulation, to the design and discovery of innovative solutions.
Photoacoustic (PA) imaging uses photon-phonon conversion for high-resolution tomography of biological tissues and functions. Exogenous contrast agents are often added to improve the image quality, but the interference from endogenous molecules diminishes the imaging sensitivity and specificity. We report a background-free PA imaging technique based on the active modulation of PA signals via magnetic alignment of Fe3O4@Au hybrid nanorods. Switching the field direction creates enhanced and deactivated PA imaging modalities, enabling a simple pixel subtraction to effectively minimize background noises. Under an alternating magnetic field, the nanorods exhibit PA signals of coherently periodic changes that can be converted into a sharp peak in a frequency domain via the fast Fourier transform. Automatic pixel-wise screening of nanorod signals performed using a computational algorithm across a time-sequence set of PA images regenerates a background-free PA image with significantly improved contrast, specificity, and fidelity.
Magnetic hyperthermia (MHT) is a therapeutic modality for the treatment of solid tumors that has now accumulated more than 30 years of experience. In the ongoing MHT clinical trials for the treatment of brain and prostate tumors, iron oxide nanoparticles are employed as intra-Tumoral MHT agents under a patient-safe 100 kHz alternating magnetic field (AMF) applicator. Although iron oxide nanoparticles are currently approved by FDA for imaging purposes and for the treatment of anemia, magnetic nanoparticles (MNPs) designed for the efficient treatment of MHT must respond to specific physical-chemical properties in terms of magneto-energy conversion, heat dose production, surface chemistry and aggregation state. Accordingly, in the past few decades, these requirements have boosted the development of a new generation of MNPs specifically aimed for MHT. In this review, we present an overview on MNPs and their assemblies produced via different synthetic routes, focusing on which MNP features have allowed unprecedented heating efficiency levels to be achieved in MHT and highlighting nanoplatforms that prevent magnetic heat loss in the intracellular environment. Moreover, we review the advances on MNP-based nanoplatforms that embrace the concept of multimodal therapy, which aims to combine MHT with chemotherapy, radiotherapy, immunotherapy, photodynamic or phototherapy. Next, for a better control of the therapeutic temperature at the tumor, we focus on the studies that have optimized MNPs to maintain gold-standard MHT performance and are also tackling MNP imaging with the aim to quantitatively assess the amount of nanoparticles accumulated at the tumor site and regulate the MHT field conditions. To conclude, future perspectives with guidance on how to advance MHT therapy will be provided. This journal is
The use of magnetic nanoparticles (MNPs) to locally increase the temperature at the nanoscale under the remote application of alternating magnetic fields (magnetic particle hyperthermia, MHT) has become an important...
The three classical core technologies for the preservation of live mammalian biospecimens—slow freezing, vitrification and hypothermic storage—limit the biomedical applications of biospecimens. In this Review, we summarize the principles and procedures of these three technologies, highlight how their limitations are being addressed via the combination of microfabrication and nanofabrication, materials science and thermal-fluid engineering and discuss the remaining challenges. This Review examines classical methods for the preservation of mammalian biospecimens and the associated mechanisms of cryoinjury and discusses how the methods’ applicability limitations are being addressed.
Owing to the quantum confinement at the nanoscale, magnetic iron oxide nanoparticles (MIONs) consisting of magnetite and maghemite nanocrystals have unique physical properties, enabling a wide range of biomedical applications by utilizing mechanical, magnetic, chemical, and thermal effects of MIONs respectively. For example, MIONs can serve as a contrast agent for magnetic resonance imaging (MRI), convert electromagnetic energy into thermal energy for hyperthermia therapy, and carry drug/gene for targeted in vivo delivery. In this review, we discuss the recent development of MION based engineering approaches and their biomedical applications, including sensitive protein quantification, magnetic nanoparticle heating, in vivo molecular imaging, and drug delivery. The opportunities and challenges in further exploring the biomedical applications of MIONs are also briefly discussed.
Cell-based medicine has made great advances in clinical diagnosis and therapy for various refractory diseases, inducing a growing demand for cell preservation as support technology. However, the bottleneck problems in cell preservation include low efficiency and poor biocompatibility of traditional protectants. In this review, cell preservation technologies are categorized according to storage conditions: hypothermic preservation at 1 °C~35 °C to maintain short-term cell viability that is useful in cell diagnosis and transport, while cryopreservation at −196 °C~−80 °C to maintain long-term cell viability that provides opportunities for therapeutic cell product storage. Firstly, the background and developmental history of the protectants used in the two preservation technologies are briefly introduced. Secondly, the progress in different cellular protection mechanisms for advanced biomaterials are discussed in two preservation technologies. In hypothermic preservation, the hypothermia-induced and extracellular matrix-loss injuries to cells are comprehensively summarized, as well as the recent biomaterials dependent on regulation of cellular ATP level, stabilization of cellular membrane, balance of antioxidant defense system, and supply of mimetic ECM to prolong cell longevity are provided. In cryopreservation, cellular injuries and advanced biomaterials that can protect cells from osmotic or ice injury, and alleviate oxidative stress to allow cell survival are concluded. Last, an insight into the perspectives and challenges of this technology is provided. We envision advanced biocompatible materials for highly efficient cell preservation as critical in future developments and trends to support cell-based medicine.
Statement of significance
Cell preservation technologies present a critical role in cell-based applications, and more efficient biocompatible protectants are highly required. This review categorizes cell preservation technologies into hypothermic preservation and cryopreservation according to their storage conditions, and comprehensively reviews the recently advanced biomaterials related. The background, development, and cellular protective mechanisms of these two preservation technologies are respectively introduced and summarized. Moreover, the differences, connections, individual demands of these two technologies are also provided and discussed.
Cell cryopreservation is of vital significance both for transporting and storing cells before experimental/clinical use. Cryoprotectants (CPAs) are necessary additives in the preserving medium in cryopreservation, preventing cells from freeze-Thaw injuries. Traditional organic solvents have been widely used in cell cryopreservation for decades. Given the obvious damage to cells due to their undesirable cytotoxicity and the burdensome post-Thaw washing cycles before use, traditional CPAs are more and more likely to be replaced by modern ones with lower toxicity, less processing, and higher efficiency. As materials science thrives, nanomaterials are emerging to serve as potent vehicles for delivering nontoxic CPAs or inherent CPAs comparable to or even superior to conventional ones. This review will introduce some advanced nanomaterials (e.g., organic/inorganic nanoCPAs, nanodelivery systems) utilized for cell cryopreservation, providing broader insights into this developing field.
Stem cells microencapsulated in hydrogel as stem cell-hydrogel constructs have wide applications in the burgeoning cell-based medicine. Due to their short shelf life at ambient temperature, long-term storage or banking of the constructs is essential to their “off-the-shelf” ready availability needed for their widespread applications. As a high-efficiency, easy-to-operate, low-toxic and low-cost method for long-term storage of the constructs, low-cryoprotectant (CPA) vitrification has attracted tremendous attention recently. However, we found many cells in the stem cell-alginate constructs (~500 μm in diameter) could not attach to substrate post low-CPA vitrification with (~2 M penetrating CPAs). To address this problem, we introduced nano-warming via magnetic induction heating (MIH) of Fe3O4 nanoparticles to minimize recrystallization and devitrification during the warming step of the low-CPA vitrification procedure. Our results indicate that high-quality stem cell-alginate hydrogel constructs with an intact microstructure, high immediate cell survival (> 80%), and greatly improved attachment efficiency (nearly three times, 68% versus 24%) of the encapsulated cells could be obtained post-cryopreservation with nano-warming. Moreover, the cells encapsulated in the cell-hydrogel constructs post-cryopreservation maintained normal proliferation under 3D culture and retained intact biological functionality of multi-lineage differentiation. This novel low-CPA vitrification approach for cell cryopreservation enabled by the combined use of alginate hydrogel microencapsulation and Fe3O4 nanoparticles-mediated nano-warming may be valuable to facilitate widespread application of stem cells in the clinic.
An efficient heat activating mediator with an enhanced specific absorption rate (SAR) value is attained via control of the iron oxide (Fe3O4) nanoparticle size from 3 to 32 nm. The monodispersed Fe3O4 nanoparticles are synthesized via a seed-less energy efficient thermolysis technique using oleylamine and oleic acid as the multifunctionalizing agent (surfactants, solvent and reducing agent). The inductive heating properties as a function of particle size revealed a strong increase in the SAR values with increasing particle size till 28 nm that is above the superparamagnetic size. Particularly, the SAR values of ferromagnetic nanoparticles (> 16 nm) are enhanced strongly with the increase of ac magnetic field amplitude than that for the superparamagnetic (3-16 nm) nanoparticles. The enhanced SAR values in ferromagnetic regime are attributed to the synergistic contribution from the hysteresis and susceptibility loss. Specifically, the 28 nm Fe3O4 nanoparticles exhibit an enhanced SAR value of 801 W/g which is nearly an order higher than that of the commercially available nanoparticles.
Functional nanomaterial embedded lightweight polymer composites have drawn considerable attention in wide ranges of industrial applications. In addition to telecommunication and aerospace utilities, microwave absorbing materials must possess fascinating properties that ensure excellent performance- from mechanical features to functionalities. Although conducting polymer composites containing magnetic nanofillers have been utilized widely, however, choosing the fillers from the library of nanoparticles and their effective dispersion inside the matrix may limit their usage in terms of performance, stability and durability. For breaking such bottleneck, herein we explored facile bottom-up synthetic procedure to fabricate different shapes (like spherical, cubic, cluster, flower) and size controlled Fe3O4 nanoparticles, and showed the effect of shape anisotropy and size that meet the criteria on above said properties in a model PC/PVDF blend with MWCNTs as a conducting nanofillers. The superior performance in terms of microwave attenuation and mechanical properties was reported for spherically shaped Fe3O4 nanomaterials. The excellent dispersibility of small-sized nanospheres was instrumental in improved consolidated loss tangent values, attenuation constant, and impedance matching and skin depth synergistically resulting in -38 dB at 18 GHz.
Sub-100 nm hollow carbon nanospheres with thin shells are highly desirable anode materials for energy storage applications. However, their synthesis remains a great challenge with conventional strategies. In this work, we demonstrate that hollow carbon nanospheres of unprecedentedly small sizes (down to ~32.5 nm and with thickness of ~3.9 nm) can be produced on a large scale by a templating process in a unique reverse micelle system. Reverse micelles enable a spatially confined Stöber process that produces uniform silica nanospheres with significantly reduced sizes compared with those from a conventional Stöber process, and a subsequent well-controlled sol–gel coating process with a resorcinol–formaldehyde resin on these silica nanospheres as a precursor of the hollow carbon nanospheres. Owing to the short diffusion length resulting from their hollow structure, as well as their small size and microporosity, these hollow carbon nanospheres show excellent capacity and cycling stability when used as anode materials for lithium/sodium-ion batteries.
Open image in new window
Vitrification, a kinetic process of liquid solidification into glass, poses many potential benefits for tissue cryopreservation including indefinite storage, banking, and facilitation of tissue matching for transplantation. To date, however, successful rewarming of tissues vitrified in VS55, a cryoprotectant solution, can only be achieved by convective warming of small volumes on the order of 1 ml. Successful rewarming requires both uniform and fast rates to reduce thermal mechanical stress and cracks, and to prevent rewarming phase crystallization. We present a scalable nanowarming technology for 1- to 80-ml samples using radiofrequency-excited mesoporous silica–coated iron oxide nanoparticles in VS55. Advanced imaging including sweep imaging with Fourier transform and microcomputed tomography was used to verify loading and unloading of VS55 and nanoparticles and successful vitrification of porcine arteries. Nanowarming was then used to demonstrate uniform and rapid rewarming at >130°C/min in both physical (1 to 80 ml) and biological systems including human dermal fibroblast cells, porcine arteries and porcine aortic heart valve leaflet tissues (1 to 50 ml). Nanowarming yielded viability that matched control and/or exceeded gold standard convective warming in 1- to 50-ml systems, and improved viability compared to slow-warmed (crystallized) samples. Last, biomechanical testing displayed no significant biomechanical property changes in blood vessel length or elastic modulus after nanowarming compared to untreated fresh control porcine arteries. In aggregate, these results demonstrate new physical and biological evidence that nanowarming can improve the outcome of vitrified cryogenic storage of tissues in larger sample volumes.
An easy metal-ion-steered solvothermal method was developed for the one-step synthesis of monodisperse, uniform NixFe3-xO4 polycrystalline nanospheres with tunable sphere diameter (40–400 nm) and composition (0 ≤ x ≤ 0.245) via changing just Ni²⁺/Fe³⁺ molar ratio (γ). With g increased from 0:1 to 2:1, sphere diameter gradually decreased and crystal size exhibited an inversed U-shaped change tendency, followed by increased Ni/Fe atom ratio from 0% to 0.0888%. An in situ-reduction, coordination-precipitation transformation mechanism was proposed to interpret the metal-ion-steered growth. Size- and composition-dependent static magnetic and microwave absorbing properties were systematically investigated. Saturation magnetization declines with g in a Boltzmann model due to the changes of crystal size, sphere diameter, and Ni content. The coercivity reaches a maximum at g = 0.75:1 because of the critical size of Fe3O4 single domain (25 nm). Studies on microwave absorption reveal that 150–400 nm Fe3O4 nanospheres mainly obey the quarter-wavelength cancellation model with the single-band absorption; 40–135 nm NixFe3-xO4 nanospheres (0 ≤ x ≤ 0.245) obey the one and three quarter-wavelength cancellation model with the multi-band absorption. 150 nm Fe3O4 nanospheres exhibit the optimal EM wave-absorbing property with an absorbing band of 8.94 GHz and the maximum RL of −50.11 dB.
Iron oxide nanoparticles are finding an increasing number of biomedical applications as sensing or trapping platforms, therapeutic and/or diagnostic agents. Most of these applications are based on their magnetic properties, which may vary depending on the nanoparticle aggregation state and/or concentration. In this work, we assess the effect of the inter- and intra-aggregate magnetic dipolar interactions on the values of the heat dissipation power and AC hysteresis loops when increasing the nanoparticle concentration and their hydrodynamic aggregate size. We observe different effects produced by inter- (long distance) or intra-aggregate (short distance) interactions, resulting in magnetizing or demagnetizing effects, respectively. Consequently, the heat dissipation power under alternating magnetic fields strongly reflects such different interacting phenomena. Intra-aggregate results were successfully modeled by numerical simulations. A better understanding of magnetic dipolar interactions is mandatory for achieving a reliable magnetic hyperthermia response when nanoparticles are located into biological matrices.
Statement of significance:
In this manuscript, we report the successful synthesis and application of Fe3O4 nanoparticles for magnetic induction heating (MIH) to enhance rewarming of vitrification-cryopreserved human umbilical cord matrix mesenchymal stem cells (hUCM-MSCs). We found that MIH-enhanced rewarming greatly improves the survival of vitrification-cryopreserved hUCM-MSCs. Moreover, the hUCM-MSCs retain their intact stemness and multilineage potential of differentiation post cryopreservation by vitrification with the MIH-enhanced rewarming. Therefore, the novel MIH-enhanced cell vitrification is valuable to facilitate the long-term storage of adult stem cells to meet their ever-increasing demand by the burgeoning cell-based medicine.
Ultrasmall core-shell nanocarriers (NCs) are believed to be ideal candidates for biological applications, as proved by silica-based core-shell NCs that fabricated using single micelle as template. Compared with inert silica, polymers with various properties play an essential and ubiquitous role in our daily life. However, the fabrication of polymer-based NCs with ultrasmall particle size (less than 20 nm) is still very limited, which is probably hindered by the difficulty in handling the polymeric process and the soft nature of most polymers. In this study, we demonstrated the fabrication of ultrasmall single micelle@resin core-shell NCs through single micelle template method using resorcinol formaldehyde resin (RFR) as model polymers. Moreover, the fluorescent property of the ultrasmall single micelle@resin core-shell NCs could be adjusted from visible light to near-infrared through the incorporation of different dye molecules. The fluorescent single micelle@RFR core-shell NCs show extra-low cytotoxicity and great potential both in vitro and in vivo bioimaging and photothermal therapy applications.
While vitrified cryopreservation holds great promise, practical application has been limited to smaller systems (cells and thin tissues) due to diffusive heat and mass transfer limitations, which are typically manifested as devitrification and cracking failures during thaw. Here then we describe a new approach for rapidly and uniformly heating cryopreserved biospecimens with radiofrequency (RF) excited magnetic nanoparticles (mNPs). Importantly, heating rates can be increased several fold over conventional boundary heating techniques and are independent of sample size. Initial differential scanning calorimetry studies indicate that the addition of the mNPs has minimal impact on the freeze-thaw behavior of the cryoprotectant systems themselves. Then proof-of-principle experiments in aqueous and cryoprotectant solutions demonstrate the ability to heat at rates high enough to mitigate or eliminate devitrification (hundreds of °C/min) and scaled heat transfer modeling is used to illustrate the potential of this innovative approach. Finally, X-ray micro-computed-tomography (micro-CT) is investigated as a planning and quality control tool, where the density-based measurements are able to quantify changes in cryoprotectant concentration, mNP concentration, and the frozen state (i.e. crystallized versus vitrified).
The oriented attachment of magnetic nanoparticles is recognized as an
important pathway in the magnetic-hyperthermia cancer treatment roadmap, thus,
understanding the physical origin of their enhanced heating properties is a crucial task
for the development of optimized application schemes. Here, we present a detailed
theoretical analysis of the hysteresis losses in dipolar-coupled magnetic nanoparticle
assemblies as a function of both the geometry and length of the array, and of the
orientation of the particles’ magnetic anisotropy. Our results suggest that the chain-like
arrangement biomimicking magnetotactic bacteria has the superior heating performance,
increasing more than 5 times in comparison with the randomly distributed system when aligned with the magnetic field.
The size of the chains and the anisotropy of the particles can be correlated with the applied magnetic field in order to have
optimum conditions for heat dissipation. Our experimental calorimetrical measurements performed in aqueous and agar gel
suspensions of 44 nm magnetite nanoparticles at different densities, and oriented in a magnetic field, unambiguously demonstrate
the important role of chain alignment on the heating efficiency. In low agar viscosity, similar to those of common biological
media, the initial orientation of the chains plays a minor role in the enhanced heating capacity while at high agar viscosity, chains
aligned along the applied magnetic field show the maximum heating. This knowledge opens new perspectives for improved
handling of magnetic hyperthermia agents, an alternative to conventional cancer therapies.
Progress in the prediction and optimization of the heating of magnetic
nanoparticles in an alternating magnetic fi eld is highly desirable for their
application in magnetic hyperthermia. Here, a model system consisting of
metallic iron nanoparticles with a size ranging from 5.5 to 28 nm is extensively
studied. Their properties depend strongly on their size: behaviors
typical of single-domain particles in the superparamagnetic regime, in the
ferromagnetic regime, and of multi-domain particles are observed. Ferromagnetic
single-domain nanoparticles are the best candidates and display
the highest specifi c losses reported in the literature so far (11.2 ± 1 mJ g − 1 ).
Measurements are analysed using recently demonstrated analytical formulas
and numerical simulations of the hysteresis loops. Several features expected
theoretically are observed for the fi rst time experimentally: i) the correlation
between the nanoparticle diameter and their coercive fi eld, ii) the correlation
between the amplitude of the coercive fi eld and the losses, and iii) the
variation of the optimal size with the amplitude of the magnetic fi eld. None
of these features are predicted by the linear response theory – generally used
to interpret hyperthermia experiments – but are a natural consequence of
theories deriving from the Stoner–Wohlfarth model; they also appear clearly
in numerical simulations. These results open the path to a more accurate
description, prediction, and analysis of magnetic hyperthermia.
Nanoporous and monodispersed Fe3O4 aggregated spheres with high surface area and oriented attachment structure have been successfully prepared by a polyol reduction process. The structure and morphology of the Fe3O4 particles were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and N2 adsorption−desorption technique. The spherical aggregates are formed by the assembling among the Fe3O4 primary nanoparticles (5 nm), and the average size of the spherical particles is around 100 nm. The nanopores are less than 3 nm in the aggregated spheres. Besides, the magnetic properties of these nanoporous particles are also investigated and the magnetization saturation value is about 42.8 emu/g.