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Biophysical Interaction of Gold Nanoparticles with Model Biological Membranes: Investigation of the Effect of Geometry on Cellular Uptake and Photothermal Performance
Cancer remains one of the most challenging health issues globally, demanding innovative therapeutic approaches for effective treatment. Nanoparticles, particularly those composed of gold, silver, and iron oxide, have emerged as promising candidates for changing cancer therapy. This comprehensive review demonstrates the landscape of nanoparticle‐based oncological interventions, focusing on the remarkable advancements and therapeutic potentials of gold, silver, and iron oxide nanoparticles. Gold nanoparticles have garnered significant attention for their exceptional biocompatibility, tunable surface chemistry, and distinctive optical properties, rendering them ideal candidates for various cancer diagnostic and therapeutic strategies. Silver nanoparticles, renowned for their antimicrobial properties, exhibit remarkable potential in cancer therapy through multiple mechanisms, including apoptosis induction, angiogenesis inhibition, and drug delivery enhancement. With their magnetic properties and biocompatibility, iron oxide nanoparticles offer unique cancer diagnosis and targeted therapy opportunities. This review critically examines the recent advancements in the synthesis, functionalization, and biomedical applications of these nanoparticles in cancer therapy. Moreover, the challenges are discussed, including toxicity concerns, immunogenicity, and translational barriers, and ongoing efforts to overcome these hurdles are highlighted. Finally, insights into the future directions of nanoparticle‐based cancer therapy and regulatory considerations, are provided aiming to accelerate the translation of these promising technologies from bench to bedside.
The increasing emphasis on the progress of nanotechnology holds significant potential for transforming the field of nanomaterials (NMs) and its impact on biomedicine. Nanotechnology has two subfields that concentrate on the phenomena, processes, and engineering at the nano–bio interface: nanotoxicology and nanomedicine. Enhancing the effectiveness of nanomedicine and increasing disease diagnostics depend critically on our understanding of the interactions among NMs and biological systems. As a result, both weak and strong driving forces at the nano–bio interface may cause structural reconfiguration, reduce bioactivity, cause the NM to malfunction, and/or cause redox interactions with biological molecules. All of these effects may have unanticipated and undesired biological effects. Novel biointerface engineering drug delivery nanosystems for cancer therapy are described, together with their prospects and problems. Here, we discussed the fundamental mechanisms controlling the reactions between the nanomaterial-biology (nano–bio) interfaces. Significance of understanding nano–bio interaction and enhancing its activity with traditional herbal medicine, thereby reducing the adverse effects and increasing the pharmacological action. We have also summarized about forecasting of nano–bio interaction with the aid of artificial intelligence. We believe that as the field of nanomedicine improves and our understanding of nano–bio interactions advances, individuals will find it easier to exploit nanomedicine.
Owing to the unique quantum size effect and surface effect, gold-based nanomaterials (GNMs) are promising for pathogen detection and broad-spectrum antimicrobial activity. This review summarizes recent research on GNMs as sensors for detecting pathogens and as tools for their elimination. Firstly, the need for pathogen detection is briefly introduced with an overview of the physicochemical properties of gold nanomaterials. And then strategies for the application of GNMs in pathogen detection are discussed. Colorimetric, fluorescence, surface-enhanced Raman scattering (SERS) techniques, dark-field microscopy detection and electrochemical methods can enable efficient, sensitive, and specific pathogen detection. The third section describes the antimicrobial applications of GNMs. They can be used for antimicrobial agent delivery and photothermal conversion and can act synergistically with photosensitizers to achieve the precise killing of pathogens. In addition, GNMs are promising for integrated pathogen detection and treatment; for example, combinations of colorimetric or SERS detection with photothermal sterilization have been demonstrated. Finally, future outlooks for the applications of GNMs in pathogen detection and treatment are summarized.
Graphical Abstract
Homogeneous distribution and adequate accumulation of photosensitizer in tumor are essential for effective photodynamic therapy (PDT). However, the intricate tumor microenvironment (TME) often poses great challenges to the deep penetration and retention of therapeutic agents in tumor. Moreover, the important effect of PDT to induce specific antitumor immune response is impeded by multiple immunosuppressive mechanisms within TME. Confronting these issues, here a rationally designed nanosystem (SUN‐NPA) with acid‐responsive sphere‐to‐fiber transformation ability by leveraging the characters of drug molecules is proposed to achieve self‐delivery of photosensitizer Chlorin e6 (Ce6) and two small‐molecule immunomodulators, metformin (MET) and sunitinib (SUN). The spatiotemporal controlled transformation enables homogeneous distribution and high accumulation of drugs to achieve enduring PDT and complete tumor elimination. Meanwhile, the co‐delivered MET and SUN alleviate tumor immunosuppression from multiple aspects, effectively synergizing with PDT to ignite potent host immune response and long‐lasting immunological memory against tumor cells. The artful integration of enhanced PDT and activated antitumor immunity realized by SUN‐NPA leads to the significant inhibition of tumor growth and metastasis, exhibiting great potential for oncotherapy.
Microrobots are of significant interest due to their smart transport capabilities, especially for precisely targeted delivery in dynamic environments (blood, cell membranes, tumor interstitial matrixes, blood–brain barrier, mucosa, and other body fluids). To perform a more complex micromanipulation in biological applications, it is highly desirable for microrobots to be stimulated with multiple stimuli rather than a single stimulus. Herein, the biodegradable and biocompatible smart micromotors with a Janus architecture consisting of PrecirolATO 5 and polycaprolactone compartments inspired by the anisotropic geometry of tadpoles and sperms are newly designed. These bioinspired micromotors combine the advantageous properties of polypyrrole nanoparticles (NPs), a high near-infrared light-absorbing agent with high photothermal conversion efficiency, and magnetic NPs, which respond to the magnetic field and exhibit multistimulus-responsive behavior. By combining both fields, we achieved an “on/off” propulsion mechanism that can enable us to overcome complex tasks and limitations in liquid environments and overcome the limitations encountered by single actuation applications. Moreover, the magnetic particles offer other functions such as removing organic pollutants via the Fenton reaction. Janus-structured motors provide a broad perspective not only for biosensing, optical detection, and on-chip separation applications but also for environmental water treatment due to the catalytic activities of multistimulus-responsive micromotors.
The current lack of insight into nanoparticle-cell membrane interactions hampers smart design strategies and thereby the development of effective nanodrugs. Quantitative and methodical approaches utilizing cell membrane models offer an opportunity to unravel particle-membrane interactions in a detailed manner under well controlled conditions. Here we use total internal reflection microscopy for real-time studies of the non-specific interactions between nanoparticles and a model cell membrane at 50 ms temporal resolution over a time course of several minutes. Maintaining a simple lipid bilayer system across conditions, adsorption and desorption were quantified as a function of biomolecular corona, particle size and fluid flow. The presence of a biomolecular corona reduced both the particle adsorption rate onto the membrane and the duration of adhesion, compared to pristine particle conditions. Particle size, on the other hand, was only observed to affect the adsorption rate. The introduction of flow reduced the number of adsorption events, but increased the residence time. Lastly, altering the composition of the membrane itself resulted in a decreased number of adsorption events onto negatively charged bilayers compared to neutral bilayers. Overall, a model membrane system offers a facile platform for real-time imaging of individual adsorption-desorption processes, revealing complex adsorption kinetics, governed by particle surface energy, size dependent interaction forces, flow and membrane composition.
The amounts of antibiotics of anthropogenic origin released and accumulated in the environment are known to have a negative impact on local communities of microorganisms, which leads to disturbances in the course of the biodegradation process and to growing antimicrobial resistance. This mini-review covers up-to-date information regarding problems related to the omnipresence of antibiotics and their consequences for the world of bacteria. In order to understand the interaction of antibiotics with bacterial membranes, it is necessary to explain their interaction mechanism at the molecular level. Such molecular-level interactions can be probed with Langmuir monolayers representing the cell membrane. This mini-review describes monolayer experiments undertaken to investigate the impact of selected antibiotics on components of biomembranes, with particular emphasis on the role and content of individual phospholipids and lipopolysaccharides (LPS). It is shown that the Langmuir technique may provide information about the interactions between antibiotics and lipids at the mixed film surface (π–A isotherm) and about the penetration of the active substances into the phospholipid monolayer model membranes (relaxation of the monolayer). Effects induced by antibiotics on the bacterial membrane may be correlated with their bactericidal activity, which may be vital for the selection of appropriate bacterial consortia that would ensure a high degradation efficiency of pharmaceuticals in the environment.
Nanoparticles (NPs), owing to their ultrasmall size, have been extensively researched for potential applications in biomedicine. During their delivery and functionalization within the organism, they frequently interact with cells. The resulting nano-bio interfaces between the NPs and cell membrane play an important role in dominating the physiological effects of NPs. Therefore, understanding how the properties of NPs affect their nano-bio interface interactions with the cell membrane is important. Compared to experimental and theoretical analyses, simulations can provide atomic-level accuracy regarding dynamic changes in structure, which can reveal the mechanisms of nano-bio interface interactions for feasible modulation. Thus, we reviewed the current advances in nano-bio interfaces from the perspective of simulations. This study will determine how the properties of NPs affect their interactions with cell membranes to provide insights for the design of NPs and summarize their corresponding biomedical applications.
Gold nanorods (GNRs) exhibit promising potentials in therapeutics and diagnostics. A quartz crystal microbalance with dissipation (QCM-D) monitoring was used to study the influence of size and solution chemistry on the deposition of GNRs on a model cell membrane. Supported lipid bilayers (SLBs) comprising zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine were used as the model cell membrane. QCM-D results showed that the deposition mass of GNRs on SLBs increased with increasing GNR concentration from 1 to 50 μM. The GNRs with smaller size exhibited a higher deposition mass in comparison with the larger one when they had a similar zeta potential. Additionally, pH also influenced the deposition behavior of GNRs on SLBs because of the change in their electrostatic interaction. Under neutral pH conditions, the deposition masses of GNRs on SLBs increased with increasing concentrations of NaCl, which is probably attributed to the reduced electrostatic repulsive force. However, the deposition mass of GNRs decreased over a range of CaCl 2 concentration from 0.5 to 10 mM. In this case, the GNR aggregation and electrostatic repulsion between GNRs and SLBs may occur due to the charge reversal of SLBs. The deposition kinetic showed that the final deposition mass was positively correlated with the initial deposition rate. Furthermore, a possible mechanism was proposed. This study provides a good understanding of the deposition of GNRs with cell membranes.
Molecular dynamics simulations of neutral gold nanoparticles (AuNPs) interacting with dipalmitoylphosphatidylcholine (DPPc) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPc) membranes were studied using a model system. Spontaneous membrane insertion of AuNPs did not occur on the time scale of atomistic simulations. To overcome the limitations of time scale, we used a harmonic restraining potential to force the AuNPs into the membranes. Free energy calculations indicate that a NP has to cross a free energy barrier of about 134 kJ mol ⁻¹ prior to forming a stable contact with the membrane. This energy barrier between lipids and NPs comes from the repulsion between headgroups of lipids and AuNPs. The experimental investigations indicate that, contrary to hydrophobic AuNPs, neutral AuNPs cannot form ion channels across lipid membranes. The adsorption of NPs induces the formation of a highly ordered region in phospholipid bilayers. Our simulation results propose that the cell penetration of small uncoated AuNPs does not involve energy-independent membrane translocation but rather involves the energy-dependent formation of nanoscale membrane holes or energy-dependent endocytosis.
Local enhancement of electromagnetic (EM) fields near dielectric and metallic surfaces is usually associated with the existence of a confined EM wave at least in one direction. This phenomenon finds applications in enhancing optical spectroscopic signals, optical emission, nonlinear optical processes, biosensing, imaging contrast and superresolution, photovoltaics response, local heating, photocatalysis, and enhanced efficiency of optoelectronic devices. A well-known example is when the surface electromagnetic wave (SEW) is excited at the interface of two media, the field gets enhanced normally to that interface. This article reviews the different configurations revealing enhanced EM fields, particularly those giving ultrahigh enhancement, such as when a localized SEW is excited not from free space but via an extended SEW. Of particular interest are surface plasmon waves (SPWs) excited at the surface of metal-dielectric and particularly when exciting localized SPWs using extended ones. The latter case so far gave the highest local field enhancement; however, configurations involving Bloch SEWs, guided mode resonances, and cavity resonances have also been shown to give significant enhancement when used to excite localized surface plasmons. With this strategy, field enhancement by more than an order of magnitude can be attained. Using this ultrahigh enhancement, the strong coupling experiments between molecules and the intense optical field will be possible and new devices may emerge from those new methodologies for ultrahigh sensitive sensing for environmental and medical applications, as well as for improved optoelectronic devices.
Gold nanomaterials have attracted considerable interest as vehicles for intracellular drug delivery. In our study, we synthesized three different shapes of methylpolyethylene glycol coated-anisotropic gold nanoparticles: stars, rods, and triangles. The cellular internalization of these nanoparticles by RAW264.7 cells was analyzed, providing a parametric evaluation of the effect of shape. The efficiency of cellular uptake of the gold nanoparticles was found to rank in the following order from lowest to highest: stars, rods, and triangles. The possible mechanisms of cellular uptake for the three types of gold nanoparticles were examined, and it was found that different shapes tended to use the various endocytosis pathways in different proportions. Our study, which has demonstrated that shape can modulate the uptake of nanoparticles into RAW264.7 cells and that triangles were the shape with the most efficient cellular uptake, provides useful guidance toward the design of nanomaterials for drug delivery.
Lipid monolayers have been studied for over a hundred years, but in the last two decades there has been a dramatic evolution, driven by a substantial development of modern characterization tools and microscopic techniques; and the lipid monolayers have successfully proved the incredible
interplay between results in model membranes and those on cell membranes continuing to this day. Together with a robust development of another model studies such as the vesicles in the bulk solution or the vesicles being fused on the solid-supported substrate to form the bilayers, the monolayer
model has never lost its scientific importance but also become an indispensable resource of fundamental information on the structures, the phase transitions, the mechanical properties of the membranes. In this review, the needs of Langmuir monolayers for understanding of the cell membranes
are described in detail, including the advantages of monolayers over the other model studies, the common experimental techniques, and the possible approaches to design the Langmuir monolayer models corresponding to the particular aspects that are observed and studied from the natural cells.
Nanoporous gold with networks of interconnected ligaments and highly porous structure holds stimulating technological implications in fuel cell catalysis. Current syntheses of nanoporous gold mainly revolve around de-alloying approaches that are generally limited by stringent and harsh multistep protocols. Here we develop a one-step solution phase synthesis of zero-dimensional hollow nanoporous gold nanoparticles with tunable particle size (150-1,000 nm) and ligament thickness (21-54 nm). With faster mass diffusivity, excellent specific electroactive surface area and large density of highly active surface sites, our zero-dimensional nanoporous gold nanoparticles exhibit ~1.4 times enhanced catalytic activity and improved tolerance towards carbonaceous species, demonstrating their superiority over conventional nanoporous gold sheets. Detailed mechanistic study also reveals the crucial heteroepitaxial growth of gold on the surface of silver chloride templates, implying that our synthetic protocol is generic and may be extended to the synthesis of other nanoporous metals via different templates.
Currently a popular area in nanomedicine is the implementation of plasmonic gold nanoparticles for cancer diagnosis and photothermal therapy, attributed to the intriguing optical properties of the nanoparticles. The surface plasmon resonance, a unique phenomenon to plasmonic (noble metal) nanoparticles leads to strong electromagnetic fields on the particle surface and consequently enhances all the radiative properties such as absorption and scattering. Additionally, the strongly absorbed light is converted to heat quickly via a series of nonradiative processes. In this review, we discuss these important optical and photothermal properties of gold nanoparticles in different shapes and structures and address their recent applications for cancer imaging, spectroscopic detection and photothermal therapy.
Monoclonal antibodies are used in numerous therapeutic and diagnostic applications; however, their efficacy is contingent on specificity and avidity. Here, we show that presentation of antibodies on the surface of nonspherical particles enhances antibody specificity as well as avidity toward their targets. Using spherical, rod-, and disk-shaped polystyrene nano- and microparticles and trastuzumab as the targeting antibody, we studied specific and nonspecific uptake in three breast cancer cell lines: BT-474, SK-BR-3, and MDA-MB-231. Rods exhibited higher specific uptake and lower nonspecific uptake in all cells compared with spheres. This surprising interplay between particle shape and antibodies originates from the unique role of shape in determining binding and unbinding of particles to cell surface. In addition to exhibiting higher binding and internalization, trastuzumab-coated rods also exhibited greater inhibition of BT-474 breast cancer cell growth in vitro to a level that could not be attained by soluble forms of the antibody. The effect of trastuzumab-coated rods on cells was enhanced further by replacing polystyrene particles with pure chemotherapeutic drug nanoparticles of comparable dimensions made from camptothecin. Trastuzumab-coated camptothecin nanoparticles inhibited cell growth at a dose 1,000-fold lower than that required for comparable inhibition of growth using soluble trastuzumab and 10-fold lower than that using BSA-coated camptothecin. These results open unique opportunities for particulate forms of antibodies in therapeutics and diagnostics.
Lipid bilayers are biomembranes common to cellular life and constitute a continuous barrier between cells and their environment. Understanding the interaction of nanoparticles with lipid bilayers is an important step toward predicting subsequent biological effects. In this study, we assessed the affinity of functionalized gold nanoparticles (Au NPs) with sizes from 5 to 100 nm to lipid bilayers by determining the Au NP distribution between aqueous electrolytes and lipid bilayers. The Au NP distribution to lipid bilayers reached an apparent steady state in 24 h with smaller Au NPs distributing onto lipid bilayers more rapidly than larger ones. Au NPs distributed to lipid bilayers to a larger extent at lower pH. Tannic acid-functionalized Au NPs exhibited greater distribution to lipid bilayers than polyvinylpyrrolidone-functionalized Au NPs of the same size. Across the various Au NP sizes, we measure the lipid bilayer-water distribution coefficient (K(lipw) = C(lip)/C(w)) as 450 L/kg lipid, which is independent of dosimetric units. This work suggests that the nanoparticle-cell membrane interaction is dependent on solution chemistry and nanoparticle surface functionality. The K(lipw) value may be used to predict the affinity of spherical Au NPs across a certain size range toward lipid membranes.
Monodisperse samples of silver nanocubes were synthesized in large quantities by reducing silver nitrate with ethylene glycol
in the presence of poly(vinyl pyrrolidone) (PVP). These cubes were single crystals and were characterized by a slightly truncated
shape bounded by {100}, {110}, and {111} facets. The presence of PVP and its molar ratio (in terms of repeating unit) relative
to silver nitrate both played important roles in determining the geometric shape and size of the product. The silver cubes
could serve as sacrificial templates to generate single-crystalline nanoboxes of gold: hollow polyhedra bounded by six {100}
and eight {111} facets. Controlling the size, shape, and structure of metal nanoparticles is technologically important because
of the strong correlation between these parameters and optical, electrical, and catalytic properties.
Breast cancer is one of the fatal diseases renowned worldwide. Chemotherapy is not sufficient for the treatment of breast cancer in a significant number of cases. In this study, we present the doxorubicin (DOX) and gold nanoparticles (AuNPs) loaded nanostructured lipid carriers (DOX+AuNPs)@NLCs, designed for dual chemo/photothermal therapy. Different geometries of AuNPs (gold nanospheres (AuNSs), gold nanorods (AuNRs), and gold nanocubes (AuNCs)) were also loaded in NLCs to exploit their photothermal heating capacity and to conceptualize the most efficient combination of drug delivery system for combined therapy. The light-triggered on-demand release of DOX from NLCs was examined before and after NIR irradiation (808 nm). The highest heating potential was obtained via AuNRs with ∆T=22 o C in 5 min with µg Au/mg lipid. The cytotoxic effect of these formulations was evaluated on MDA-MB-231 breast cancer cells and the highest growth inhibition (81%) is achieved with (DOX+AuNRs)@NLC under 5 min NIR application. It is found that the geometry directly effects the photothermal capability of AuNPs, a synergistic interaction between cytotoxic action of DOX and local hyperthermia provided by AuNPs can significantly enhance the skills on the irreversible cellular damage and developed state-of-art formulations hold a great potential as a combined-cancer-therapy agent. Thus, this study offers promise for the development of a lipid-based nano-platform that is biocompatible, multifunctional, and can be utilized for combined therapy, with tunable properties.
Customizable gold nanoparticle platforms are motivating innovations in drug discovery with massive therapeutic potential due to their biocompatibility, stability, and imaging capabilities. Further development requires the understanding of how discrete differences in shape, charge, or surface chemistry affect the drug delivery process of the nanoparticle. The nanoparticle shape can have a significant impact on nanoparticle function as this can, for example, drastically change the surface area available for modifications, such as surface ligand density. In order to investigate the effects of nanoparticle shape on the structure of cell membranes, we directly probed nanoparticle–lipid interactions with an interface sensitive technique termed sum frequency generation (SFG) vibrational spectroscopy. Both gold nanostars and gold nanospheres with positively charged ligands were allowed to interact with a model cell membrane and changes in the membrane structure were directly observed by specific SFG vibrational modes related to molecular bonds within the lipids. The SFG results demonstrate that the +Au nanostars both penetrated and impacted the ordering of the lipids that made up the membrane, while very little structural changes to the model membrane were observed by SFG for the +Au nanospheres interacting with the model membrane. This suggests that the +Au nanostars, compared to the +Au nanospheres, are more disruptive to a cell membrane. Our findings indicate the importance of shape in nanomaterial design and provide strong evidence that shape does play a role in defining nanomaterial-biological interactions.
Nanoparticles have been extensively adopted to deliver therapeutic drug molecules to cells through clathrin-mediated endocytosis (CME). The size and shape of nanoparticles are important factors in the design of a drug delivery system. Both the clathrin coat and actin force induce the bending of the membrane during CME. However, due to the complex coupled effects of size, shape, and surface properties, nanoparticle shape effects are difficult to elucidate through experiments. Herein, we establish a comprehensive framework considering both the actin force and the dynamic assembly of the clathrin coat. To explore the effect of the nanoparticle size and shape on CME, we construct a clathrin coat growth model with actin force feedback. The clathrin coat growth model, nanoparticle internalization efficiency, and transportation efficiency are discussed through numerical analysis. The transportation efficiency is defined by the energy cost of the cell absorbing unit dose target drug. Numerical results illustrate that the proposed clathrin coat growth model is consistent with the actual physiological process, especially for CME considering receptor-mediated effects. The elliptical nanoparticle exhibits higher internalization and transportation efficiencies. A larger nanoparticle has lower internalization efficiency but higher transportation efficiency. Our results demonstrate that the internalization and transportation efficiencies of nanoparticles with an intermediate aspect ratio are higher than those with low or high aspect ratios. Our model provides insight into the intrinsic mechanism of CME and useful guidance for the practical design of the size and shape of nanoparticles for biopharmaceutical research.
In the drug delivery field, there is beyond doubt that the shape of micro- and nanoparticles (M&NPs) critically affects their biological fate. Herein, following an introduction describing recent technological advances for designing nonspherical M&NPs, we highlight the role of particle shape in cell capture, subcellular distribution, intracellular drug delivery, and cytotoxicity. Then, we discuss theoretical approaches for understanding the shape effect on particle internalization by the cell membrane. Subsequently, recent advances on shape-dependent behaviors of M&NPs in the systemic circulation were detailed. In particular, the interaction of M&NPs with blood proteins, biodistribution, and circulation under flow conditions were analyzed. Finally, the hurdles and future directions for developing nonspherical M&NPs were underscored.
The bioactivity, biological fate and cytotoxicity of nanomaterials when they come into contact with living organisms are determined by their interaction with biomacromolecules and biological barriers. In this context, the role of symmetry/shape anisotropy of both the nanomaterials and biological interfaces in their mutual interaction, is a relatively unaddressed issue. Here, we study the interaction of gold nanoparticles (NPs) of different shapes (nanospheres and nanorods) with biomimetic membranes of different morphology, i.e. flat membranes (2D symmetry, representative of the most common plasma membrane geometry), and cubic membranes (3D symmetry, representative of non-lamellar membranes, found in Nature under certain biological conditions). For this purpose we used an ensemble of complementary structural techniques, including Neutron Reflectometry, Grazing Incidence Small-Angle Neutron Scattering, on a nanometer lengthscale and Confocal Laser Scanning Microscopy on a micrometer length scale. We found that the structural stability of the membrane towards NPs is dependent on the topological characteristic of the lipid assembly and of the NPs, where a higher symmetry gave higher stability. In addition, Confocal Laser Scanning Microscopy analyses highlighted that NPs interact with cubic and lamellar phases according to two distinct mechanisms, related to the different structures of the lipid assemblies. This study for the first time systematically addresses the role of NPs shape in the interaction with lipid assemblies with different symmetry. The results will contribute to improve the fundamental knowledge on lipid interfaces and will provide new insights on the biological function of phase transitions as a response strategy to the exposure of NPs.
Gold nanoparticles have been intensively studied in cancer therapy to improve drug release, increasing therapeutic action and reducing adverse effects. The interaction between gold nanoparticles and cell membranes can give information about the cell internalization. In this study, gold nanoparticles with aminolevulinic acid (5-ALA) were synthesized using the photoreduction method (5-ALA: AuNPs). The prodrug 5-ALA is responsible for protoporphyrin IX synthesis inside the cell and allows the use of therapies as photodynamic and sonodynamic therapies. The cytotoxicity test was performed on a breast cancer tumor line (MCF-7), and high Content Screening assay was applied to evaluate the entry of nanoparticles into cells. DPPS Langmuir monolayers were assembled at the air/water interface and employed as a simplified membrane model for half of a tumorigenic cell membrane. We assessed the molecular interactions between 5-ALA: AuNPs and phospholipids using tensiometry (π-A isotherms) and vibrational spectroscopy (PM-IRRAS) experiments. We found that the functionalized gold nanoparticles strongly interact with DPPS polar head groups (especially phosphate and carbonyl), changing the phospholipid hydration and leading to a general decrease in the monolayer conformational order. This work then probes that specific interaction between 5-ALA: AuNPs and the negatively charged phospholipid can be assessed using Langmuir monolayers as simplified biomembrane models.
The biophysical interaction between the nanoparticles (NPs) and biological interfaces is vitally important due to the increasing usage of NPs in biomedical and pharmaceutical applications such as drug delivery. Several different approaches or ligands can be utilized including surfactants for the surface decoration of NPs. We used two custom-made, positively charged and double-tailed surfactants which were hydrocarbon-based HHL (Hydrocarbon-Hydrocarbon Lipid) and fluorocarbon-hydrocarbon-based hybrid FHL (Fluorocarbon-Hydrocarbon Lipid) molecules to decorate the surface of negatively charged citrate-capped gold NPs (cit-AuNPs). Two model membranes were used throughout the study that were 1,2-dipalmitoyl-sn-glycero-3-phosphocoline (DPPC) and Endothelium model membrane (EMM). It was determined that although FHL and HHL have similar hydrophobicity, the lipophobicity of the fluorocarbon chain in the structure of FHL facilitates the interaction of AuNPs with model membranes and promotes the uptake of the particles. For EMM, it was observed that, the introduction of FHL-AuNPs provided 28 mN/m increase on π whereas HHL-AuNPs and CTAB-AuNPs gave rise to 12 mN/m and 7 mN/m, respectively, at constant area. In spite of the results obtained from DPPC and EMM monolayers were in similar trend, it is observed that the interaction of NPs with the membranes does not exhibit identical patterns signifying the need of using natural composition of lipids. As a result, hereby the vital parameters about the surface chemistry that influence the cellular uptake and the effect of AuNPs on the natural behavior of cell membranes were systematically examined which could be quite informative in designing a versatile and efficient nanocarrier system for drug delivery applications.
Gold nanoparticles (GNPs) indicate potential in the development of cancer treatments as vehicles for thermal damage of cancer cells because of their photothermal heating capability. Herein, we aim to investigate the effect of GNPs geometry as photothermal transducers on cellular uptake and photothermal therapy (PTT) efficacy.
For this aim, seven different shapes of anisotropic GNPs: stars, hollow, rods, cages, spheres, Fe-Au, and Si-Au core shells were synthesized and investigate the effect of shape on GNPs optical properties. The physic-chemical characterization of prepared GNPs was investigated by UV-Vis, DLS-Zeta, and TEM analysis. The effect of GNPs geometry on cellular uptake was investigated by ICP-MS and flow cytometry method. The PTT potential of these GNPs was compared on MCF7 cells in vitro using MTT assay, cell cycle, and Annexin-V apoptosis assay.
While all these GNPs could absorb and convert near-infrared light into heat, gold nanostars exhibited the lowest cytotoxicity, highest cellular uptake and highest heat generation compared to other structures. Following photothermal treatment, due to substantial heat producing in MCF7 cells, the apoptosis induction rate was greatly increased for all anisotropic gold nanostructures (stars, hollow, rods, and cages) especially gold nanostars.
Combined, we can conclude that GNPs geometry affects cellular uptake and heat generation amount as well as cell destruction by apoptosis pathway and the gold nanostar is promising candidates for photothermal destruction.
Background
The use of functionalized iron oxide nanoparticles of various chemical properties and architectures offers a new promising direction in gene delivery and silencing, cellular imaging and cancer imaging and treatment. The increasing applications of nanoparticles in medicine require that these engineered nanomaterials will come in contact with human cells without damaging essential tissues. Thus, efficient delivery must be achieved while minimizing cytotoxicity during passage through cell membranes to reach intracellular target compartments.
Methods
Differential Scanning Calorimetry (DSC) and atomistic Molecular Dynamics (MD) simulations were performed for two magnetite nanoparticles with different coatings, in order to assess their different interactions with model dipalmitoylphosphatidylcholine (DPPC) membranes. The magnetite core was functionalized with polyvinyl alcohol (PVA) and polyarabic acid (ARA).
Results
DSC experiments showed that both nanoparticles interact with the DPPC lipid bilayer, albeit to a different degree, which was further verified and quantified by MD simulations. The two model systems were simulated, and dynamical and structural properties were monitored.
Conclusions
Our findings demonstrate that functionalized magnetite nanoparticles interact strongly with the DPPC lipid bilayers and that the interactions of the nanoparticles are strongly related to their surface coatings. DSC in combination with MD simulations is a promising strategy to assess the physicochemical interactions of coated nanoparticles with lipid bilayers.
General significance
Understanding the physico-chemical interactions of different nanoparticle coatings in contact with model cell membranes is the first step for assessing toxic response and could lead to predictive models for estimating toxicity. Our findings demonstrate that the external coating is a key factor for identifying promising nanoparticle platforms for theranostic applications.
Nanomaterial contamination in the environment poses severe threats to public health and wellness. Understanding interactions between nanoparticles and biomembranes is pivotal to understanding the physiological effects of nanomaterials. The prevailing understanding is that a protein corona forms around nanoparticles upon their entering biological systems. The effect of the protein corona on the membrane-nanoparticle interaction has not been comprehensively investigated. Here, we report a systematic study to better understand the effects of the protein corona on nanoparticle-biomembrane interactions with both plasma membranes (293T cell line) and biomimetic membranes. Giant plasma membrane vesicles (GPMVs) and giant unilamellar vesicles (GUVs) fabricated from organ lipid extracts (brain, heart, and liver) served as biomimetic models in our study. Reduced charged-nanoparticle adhesion to both plasma and biomimetic membranes with the presence of the protein corona suggests that the protein corona interferes with the electrostatic interaction between nanoparticles and biomembranes. These similar trends of nanoparticle adhesion among the membranes indicated that model membranes can capture this electrostatic interaction with similar responses as plasma membranes. However, the membrane integrity subsequent to the interaction was different between the two systems, indicating the limitations of model membranes in recreating the complexity and dynamics of plasma membranes. As the first systematic study correlating nanoparticle interactions with cell membranes, isolated cell membranes, and synthetic vesicles from natural lipid extracts, we demonstrated that biomimetic membranes can serve as excellent analogues to cell membranes in providing fundamental insights regarding the electrostatic interaction between nanoparticles and biomembranes.
Using the same synthesis method, which was stopped at different time intervals, gold nanoparticles (Au NPs) with different shapes, from spherical to bone-shaped, were obtained. The physical properties of the synthesized Au NPs were investigated using transmission electron microscopy (TEM) combined with selected area electron diffraction patterns (SAED) and ultraviolet-visible spectroscopy (UV-vis). The TEM images showed, that stopping the synthesis after one minute lead to the formation of small spherical Au NPs, which evolved to the cubic shape, rods and bone-shaped Au NPs after 15 min, 30 min, 2 h, respectively. SAED patterns showed, that all the obtained Au NPs were crystalline. UV-vis spectra revealed, that the light absorbance depends on the shape of the Au NPs. Moreover, the effects of the time factor in the formation of Au NPs on the effective conversion of electromagnetic energy into thermal energy, was studied. Furthermore, simulated photothermal therapy (PTT) in combination with the obtained NPs, was done for two cancer cell lines SW480 and SW620. The mortality of cells after using the differently shaped Au NPs as photosensitizers is between 18 % and 52 % and increases with the decrease of the synthesis time.
With increasing industrial and biomedical applications of engineered nanomaterials (ENMs), concerns have been raised regarding increased risk of exposure. Exposure to ENMs can potentially lead to adverse health effects including cell toxicity. Plasma membrane, a lipid bilayer surrounding all cells, is the first cellular entity that comes into contact with foreign particles and membrane damage by ENMs is one of the potential mechanisms through which ENMs induce cytotoxicity. In recent years, significant effort has been focused on elucidating the complex interactions at the particle-plasma membrane interface. Such studies have primarily relied on membrane models to tease out what particle physicochemical properties might perturb the structure and function of the cell plasma membrane. However, the diversity of membrane models has made it difficult to translate the results obtained from studies with one model to another and ultimately to live cells. This review summarizes the current knowledge on ENM-plasma membrane interactions based on the studies in membrane models including lipid monolayers, supported lipid bilayers, and lipid vesicles. The mechanisms of membrane disruption by the ENMs in each model have been discussed in detail and the role of the membrane model itself in modulating the results has been described. In addition, results in membrane models have been compared with the current knowledge from cells. Finally, some of the challenges toward improving the current membrane models and enhancing the environmental relevance of studies are discussed.
Understanding the interaction between nanomaterials and biological interfaces is a key unmet goal that still hampers clinical translation of nanomedicine. Here we investigate and compare non-specific interaction of gold nanoparticles (AuNPs) with synthetic lipid and wild type macrophage membranes. A comprehensive data set was generated by systematically varying the structural and physicochemical properties of the AuNPs (size, shape, charge, surface functionalization) and of the synthetic membranes (composition, fluidity, bending properties and surface charge), which allowed to unveil the matching conditions for the interaction of the AuNPs with macrophage plasma membranes in vitro. This effort directly proved for the first time that synthetic bilayers can be set to mimic and predict with high fidelity key aspects of nanoparticle interaction with macrophage eukaryotic plasma membranes. It then allowed to model the experimental observations according to classical interface thermodynamics and in turn determine the paramount role played by non-specific contributions, primarily electrostatic, Van der Waals and bending energy, in driving nanoparticle-plasma membrane interactions.
A polarization-independent metamaterial near-perfect absorber is numerically studied in the infrared range in a two-perpendicular-nanorod design. It is shown that the absorptance and the peak wavelength associated with magnetic resonance are sensitive to the nanorod length, the thickness, and the refractive index of the spacer, while only being slightly affected by the period and the distance between neighboring nanorods. This design shows two absorption peaks with absorptance values of 89% and 83% at the wavelengths of 1.24 and 1.46 μm, respectively. Furthermore, the absorptance and the peak wavelength associated with magnetic resonance show negligible dependence on the polarization angle. These properties are advantageous for applications, including thermal sensing and selective emitters in thermophotovoltaics. © 2017 Society of Photo-Optical Instrumentation Engineers (SPIE).
Physical forms of microparticles and nanoparticles, such as the size, charge, and shape, are known to affect endocytosis. Improving the physical designs of the drug carriers can increase the drug uptake efficiency and the subsequent drug efficacy. Simple shapes, such as sphere and cylinder, have been studied for their ability for endocytosis. To have a better understanding of the shape effect on cellular uptake, different particle shapes were prepared, using the keyboard character shapes, and their impacts on cellular uptake were examined. The results showed that shapes with higher aspect ratio and sharper angular features have a higher chance of adhering to the cells and become internalized by the cancer cells. The local interaction between the cell membrane and the part of the microparticle in contact with the cell membrane also plays a crucial role in determining the outcome.
This review article focuses on the physiochemical mechanisms underlying nanoparticle uptake into cells. When nanoparticles are in close vicinity to a cell, the interactions between the nanoparticles and the cell membrane generate forces from different origins. This leads to the membrane wrapping of the nanoparticles followed by cellular uptake. This article discusses how the kinetics, energetics, and forces are related to these interactions and dependent on the size, shape, and stiffness of nanoparticles, the biomechanical properties of the cell membrane, as well as the local environment of the cells. The discussed fundamental principles of the physiochemical causes for nanoparticle-cell interaction may guide new studies of nanoparticle endocytosis and lead to better strategies to design nanoparticle-based approaches for biomedical applications.
Understanding interactions between nanoparticles (NPs) with biological matter, particularly cells, is becoming increasingly important due to their growing application in medicine and materials, and consequent biological and environmental exposure. For NPs to be utilised to their full potential, it is important to correlate their functional characteristics with their physical properties, which may also be used to predict any adverse cellular responses. A key mechanism for NPs to impart toxicity is to gain cellular entry directly. Many parameters affect the behaviour of nanomaterials in a cellular environment particularly their interactions with cell membranes, including their size, shape and surface chemistry as well as factors such as the cell type, location and external environment (e.g. other surrounding materials, temperature, pH and pressure). Aside from in vitro and in vivo experiments, model cell membrane systems have been used in both computer simulations and physicochemical experiments to elucidate the mechanisms for NP cellular entry. Here we present a brief overview of the effects of NPs physical parameters on their cellular uptake, with focuses on 1) related research using model membrane systems and physicochemical methodologies; and 2) proposed physical mechanisms for NP cellular entrance, with implications to their nanotoxicity. We conclude with a suggestion that the energetic process of NP cellular entry can be evaluated by studying the effects of NPs on lipid mesophase transitions, as the molecular deformations and thus the elastic energy cost are analogous between such transitions and endocytosis. This presents an opportunity for contributions to understanding nanotoxicity from a physicochemical perspective.
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Gold nanorods were prepared via a seed-mediated sequential growth process involving the use of citrate-stabilised seed crystals and their subsequent growth in a series of reaction solutions containing [AuCl4]−, ascorbic acid and the cationic surfactant cetyltrimethylammonuim bromide (CTAB). Electron diffraction analysis and HRTEM images of mature nanorods showed superpositions of two specific pairs of crystallographic zones, either <112> and <100> or <110> and <111>, which were consistent with a cyclic penta-twinned crystal with five {111} twin boundaries arranged radially to the [110] direction of elongation. The nanorods have an idealised 3-D prismatic morphology with ten {111} end faces and five {100} or {110} side faces, or both. TEM studies of crystals at various stages of growth indicated that the seed crystals are initially transformed by growth and aggregation into decahedral penta-twinned
crystals, 4% of which become elongated when a fresh reaction solution is added, whilst the remaining twins grow isometrically. Reiteration of this procedure increases the length of the existing nanorods, induces further transformation of isometric particles to produce a second (and third) population of shorter, wider nanorods, and increases the size of the isometric crystals. The data indicate that symmetry breaking in fcc metallic structures to produce anisotropic nanoparticles is based on an intrinsic structural mechanism (twinning) that is subsequently modulated extrinsically during growth in solution by specific adsorption of AuI–surfactant complexes on the side faces/edges of the isometric penta-twinned crystals and which is responsible for the preferential growth along the common [110] axis. We propose that the coupling of multiple twinning and habit modification is a general mechanism that applies to other experimental
procedures (electrochemical, inverse micellar media) currently used to prepare metallic nanoparticles with a high aspect ratio.
In order to engineer safer nanomaterials, there is a need to understand, systematically evaluate, and develop constructs with appropriate cellular uptake and intracellular fates. The overall goal of this project is to determine the uptake patterns of silica nanoparticle geometries in model cells, in order to aid in the identification of the role of geometry on cellular uptake and transport. In our experiments we observed a significant difference in the viability of two phenotypes of primary macrophages; immortalized macrophages exhibited similar patterns. However, both primary and immortalized epithelial cells did not exhibit toxicity profiles. Interestingly uptake of these geometries in all cell lines exhibited very different time-dependent patterns. A screening of a series of chemical inhibitors of endocytosis was performed to isolate the uptake mechanisms of the different particles. The results show that all geometries exhibit very different uptake profiles and that this may be due to the orientation of the nanoparticles when they interact with the cell surface. Additionally, evidence suggests that these uptake patterns initialize different downstream cellular pathways, dependent on cell type and phenotype.
Nanotoxicity is becoming a major concern as the use of nanoparticles of different shapes in imaging, therapeutics, diagnostics, catalysis, sensing and energy harvesting continues to grow dramatically. The nature of particle-cell membrane interactions is an important determinant of toxicity. Using advanced molecular dynamics simulation techniques, we predict translocation rate constants of cone, cube, rod, rice, pyramid, and sphere-shaped nanoparticles through lipid membranes. The results indicate that depending on nanoparticle shape and surface charge density, the translocation rates can vary by over 60 orders of magnitude. Unlike isotropic nanoparticles, positively charged, faceted rice shaped nanoparticles undergo electrostatics-driven reorientation in the vicinity of the membrane to maximize their contact area and translocate instantaneously, disrupting lipid self-assembly and thereby causing significant membrane damage. In contrast, negatively charged nanoparticles are electrostatically repelled from the cell membrane and are less likely to translocate. Differences in translocation rates among various shapes may have implications on the structural evolution of pathogens from spherical to rod-like morphologies for enhanced efficacy.
We report a new approach for the seed-mediated synthesis of gold nanorods with high aspect ratios by the addition of nitric acid. Various amounts of nitric acid were added during nanorod growth to significantly enhance the production of high aspect ratio nanorods. The resulting nanorods have uniform diameters of 19−20 nm and can reach lengths of 400−500 nm to yield nanorods with average aspect ratios of 21−23. The nanorods represent a large fraction of the gold nanostructures synthesized, with triangular, truncated triangular, and hexagonal nanoplates about 120−200 nm in width making up rest of the gold nanostructures formed. These nanorods spontaneously self-assemble into a high-density three-dimensional packing structure with the nanorods arranged side-by-side and end-to-end. These nanorods possess a 5-fold twinned structure with ten {111} end faces and five {100} side faces. UV−vis absorption spectrum shows a transverse plasmon absorption band at 508 nm. The longitudinal plasmon absorption band should appear beyond 2500 nm due to the extremely long length of these nanorods. The presence of nitrate ions, rather than the slight pH change caused by nitric acid, is believed to have a greater effect on the formation of these nanorods.
Spherical and rod-shaped gold nanoparticles with surface poly(ethylene glycol) (PEG) chains were characterized for size, shape, charge, poly dispersity and surface plasmon resonance. The nanoparticles were injected intravenously to 6-8-week-old female nu/nu mice bearing orthotopic ovarian tumors, and their biodistribution in vital organs was compared. Gold nanorods were taken up to a lesser extent by the liver, had longer circulation time in the blood, and higher accumulation in the tumors, compared with their spherical counterparts. The cellular uptake of PEGylated gold nanoparticles by a murine macrophage-like cell line as a function of geometry was examined. Compared to nanospheres, PEGylated gold nanorods were taken up to a lesser extent by macrophages. These studies point to the importance of gold nanoparticle geometry and surface properties on transport across biological barriers.
Gold nanoparticles (AuNPs) are a suitable platform for development of efficient delivery systems. AuNPs can be easily synthesized, functionalized, and are biocompatible. The tunability of the AuNP monolayer allows for complete control of surface properties for targeting and stability/release using these nanocarriers. This review will discuss several delivery strategies utilizing AuNPs.
This work was supported by a 2006 NIH Pioneer Award (5DP1 OD000798). E.C.C. was also partially supported by a postdoctoral fellowship from the Korea Research Foundation (KRF-2007-357-D00070) funded by the Korean Government. Part of the research was conducted at the Nano Research Facility (NRF), a member of the National Nanotechnology Infrastructure Network (NNIN), which is supported by the NSF under award no. ECS-0335765. NRF is part of School of Engineering and Applied Science at Washington University in St. Louis.
Gold nanocubes demonstrate unique optical properties of the high photoluminescence (PL) quantum yield and a remarkably enhanced extinction band at 544 nm. The 4 x 10(-2) PL yield, which is about 200 times higher than that of gold nanorods, allows gold nanocubes to be successfully used in cell imaging of human liver cancer cells (QGY) and human embryo kidney cells (293T) with a common method of single-photon excitation. The high extinction coefficients of gold nanocubes also facilitate them carrying out the photothermal therapy of QGY and 293T cells, showing similar photokilling efficiency as compared to gold nanorods.
The aim of this study was to test the hypothesis that the molecular structure of cationic surfactants at the nanoparticle (NP) interface influences the biophysical interactions of NPs with a model membrane and cellular uptake of NPs. Polystyrene NPs (surfactant-free, 130 nm) were modified with cationic surfactants. These surfactants were of either dichained (didodecyldimethylammonium bromide [DMAB]) or single-chained (cetyltrimethylammonium bromide [CTAB] and dodecyltrimethylammonium bromide [DTAB]) forms, with the latter two having different hydrophobic chain lengths. Biophysical interactions of these surfactant-modified NPs with an endothelial cell model membrane (EMM) were studied using a Langmuir film balance. Changes in surface pressure (SP) of EMM as a function of time following interaction with NPs and in the compression isotherm (pi-A) of the lipid mixture of EMM in the presence of NPs were analyzed. Langmuir-Schaeffer (LS) films, which are EMMs that have been transferred onto a suitable substrate, were imaged by atomic force microscopy (AFM), and the images were analyzed to determine the mechanisms of the NP-EMM interaction. DMAB-modified NPs showed a greater increase in SP and a shift toward higher mean molecular area (mmA) than CTAB- and DTAB-modified NPs, indicating stronger interactions of DMAB-modified NPs with the EMM. However, analysis of the AFM phase and height images of the LS films revealed that both DMAB- and CTAB-modified NPs interacted with the EMM but via different mechanisms: DMAB-modified NPs penetrated the EMM, thus explaining the increase in SP, whereas CTAB-modified NPs anchored onto the EMM's condensed lipid domains and hence did not cause any significant change in SP. Human umbilical vein endothelial cells showed greater uptake of DMAB- and CTAB-modified NPs than of DTAB-modified or unmodified NPs. We conclude that (i) the dichained and single-chained cationic surfactants on NPs have different mechanisms of interaction with the model membrane and that (ii) NPs that demonstrate greater biophysical interactions with the membrane also show greater cellular uptake. Biophysical interactions of NPs with a model membrane thus could be effectively used for developing nanocarriers with optimized surface properties for drug delivery and imaging applications.
A seed-mediated growth method was used to control the morphology and dimensions of Au nanocrystals by the manipulation of the experimental parameters in aqueous solution at room temperature. This chemical route produces various structural architectures with rod-, rectangle-, hexagon-, cube-, triangle-, and starlike profiles and branched (such as bi-, tri-, tetra-, and multipod) Au nanocrystals of various dimensions in high yield in the presence of a single surfactant, cetyltrimethylammonium bromide.
Giant vesicles formed of 1,2-dipalmitoylphosphatidylcholine (DPPC) and sterols (cholesterol or ergosterol) in water and water/ethanol solutions have been used to examine the effect of sterol composition and ethanol concentration on the area compressibility modulus (K(a)), overall mechanical behavior, vesicle morphology, and induction of lipid alkyl chain interdigitation. Our results from micropipette aspiration suggest that cholesterol and ergosterol impact the order and microstructure of the gel (L(beta)') phase DPPC membrane. At low concentration (10-15 mol%) these sterols disrupt the long-range lateral order and fluidize the membrane (K(a) approximately 300 mN/m). Then at 18 mol%, these sterols participate in the formation of a continuous cohesive liquid-ordered (L(o)) phase with a sterol-dependent membrane density (K(a) approximately 750 for DPPC/ergosterol and K(a) approximately 1100 mN/m for DPPC/cholesterol). Finally at approximately 40 mol% both cholesterol and ergosterol impart similar condensation to the membrane (K(a) approximately 1200 mN/m). Introduction of ethanol (5-25 vol%) results in drops in the magnitude of K(a), which can be substantial, and sometimes individual vesicles with lowered K(a) reveal two slopes of tension versus apparent area strain. We postulate that this behavior represents disruption of lipid-sterol intermolecular interactions and therefore the membrane becomes interdigitation prone. We find that for DPPC vesicles with sterol concentrations of 20-25 mol%, significantly more ethanol is required to induce interdigitation compared to pure DPPC vesicles; approximately 7 vol% more for ergosterol and approximately 10 vol% more for cholesterol. For lower sterol concentrations (10-15 mol%), interdigitation is offset, but by <5 vol%. These data support the idea that ergosterol and cholesterol do enhance survivability for cells exposed to high concentrations of ethanol and provide evidence that the appearance of the interdigitated (L(beta)I) phase bilayer is a major factor in the disruption of cellular activity, which typically occurs between approximately 12 and approximately 16 vol% ethanol in yeast fermentations. We summarize our findings by producing, for the first time, "elasticity/phase diagrams" over a wide range of sterol (cholesterol and ergosterol) and ethanol concentrations.
This tutorial review presents an introduction to the field of noble metal nanoparticles and their current applications. The origin of the surface plasmon resonance and synthesis procedures are described. A number of applications are presented that take advantage of the electromagnetic field enhancement of the radiative properties of noble metal nanoparticles resulting from the surface plasmon oscillations.
Understanding the biophysical interactions of nanoparticles (NPs) with cell membranes is critical for developing effective nanocarrier systems for drug delivery applications. We developed an endothelial model cell membrane (EMM) using a mixture of lipids and Langmuir balance to study its interaction with NPs. Polystyrene NPs of different surface chemistry and sizes were used as a model nanomaterial, and changes in the membrane's surface pressure (SP) were used as a parameter to monitor its interactions with NPs. Aminated NPs (60 nm) increased SP, plain NPs reduced it, and carboxylated NPs of the same size had no effect. However, smaller NPs (20 nm) increased SP irrespective of surface chemistry, and serum did not influence their SP effect, whereas it masked the effect of larger (>60 nm) plain and carboxylated but not that of aminated NPs. Membranes formed with a single phospholipid showed a different pattern of interactions with NPs than that with EMM, signifying the need of using a mixture of lipids representing the respective cells/tissue of interest for a model membrane. The particular effect of NP characteristics on SP, determined using atomic force microscopy and pi- A (surface pressure-area) isotherm, can be explained on the basis of whether the interaction results in condensation of phospholipids (increase in SP) or their displacement from the interface into the subphase (decrease in SP), causing destabilization of the membrane. We conclude that NP characteristics significantly influence biophysical interactions with the membrane. Further, the molecular mechanism(s) of nanoparticle interactions with model membranes can be effectively used for optimizing the characteristics of nanomaterials for particular biological applications.
This paper reports on the characterization and preliminary comparison of gold nanoparticles of differing surface modification and shape when used as extrinsic Raman labels (ERLs) in high-sensitivity heterogeneous immunoassays based on surface enhanced Raman scattering (SERS). ERLs are gold nanoparticles coated with an adlayer of an intrinsically strong Raman scatterer, followed by a coating of a molecular recognition element (e.g., antibody). Three types of ERLs, all with a nominal size of approximately 30 nm, were fabricated by using spherical citrate-capped gold nanoparticles (sp-cit-Au NPs), spherical CTAB-capped gold nanoparticles (sp-CTAB-Au NPs), or cube-like CTAB-capped gold nanoparticles (cu-CTAB-Au NPs) as cores. The performance of these particles was assessed via a sandwich immunoassay for human IgG in phosphate buffered saline. The ERLs fabricated with sp-CTAB-Au NPs as cores proved to be more than 50 times more sensitive than those with sp-cit-Au NPs as cores; the same comparison showed that the ERLs with cu-CTAB-Au NPs as cores were close to 200 times more sensitive. Coupled with small differences in levels of nonspecific adsorption, these sensitivities translated to a limit of detection (LOD) of 94, 2.3, and 0.28 ng/mL, respectively, for the detection of human IgG in the case of sp-cit-Au NPs, sp-CTAB-Au NPs, and cu-CTAB-Au NPs. The LOD of the cu-CTAB-Au NPs is therefore approximately 340 times below that for the sp-cit-Au NPs. Potential applications of these labels to bioassays are briefly discussed.
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