Human blood biocompatibility and immunogenicity of scFvD2B PEGylated gold nanoparticles.

Single chain variable D2B antibody fragments (scFvD2Bs) exhibit high affinity binding to prostate specific membrane antigens overexpressed in metastatic prostate cancer (PC). Conjugation of scFvD2B to gold nanoparticles (AuNPs) would enhance its stability and plasma half-life circulation to shuttle theranostic agents in PC. In this study, we synthesized PEGylated scFvD2B-AuNPs (AuNPs-scFvD2B-PEG) and tested their integrity, biocompatibility, and immunogenicity in freshly withdrawn human blood. Prior to blood incubation, Zeta potential measurements, UV-Vis spectroscopy, and dynamic light scattering (DLS) were used to assess the physicochemical properties of our nano-complexes in the presence or absence of PEGylation. A surface plasmon resonance band shift of 2 and 4 nm confirmed the successful coating for AuNPs-scFvD2B and AuNPs-scFvD2B-PEG, respectively. Likewise, DLS revealed a size increase of ∼3 nm for AuNPs-scFvD2B and ∼19 nm for AuNPs-scFvD2B-PEG. Zeta potential increased from -34 to -19 mV for AuNPs-scFvD2B and reached -3 mV upon PEGylation. Similar assessment measures were applied post-incubation in human blood with additional immunogenicity tests, such as hemolysis assay, neutrophil function test, and pyridine formazan extraction. Interestingly, grafting PEG chains on AuNPs-scFvD2B precluded the binding of blood plasma proteins and reduced neutrophil activation level compared with naked AuNPs-citrate counterparts. Most likely, a hydrated negative PEG cloud shielded the NPs rendering blood compatiblility with less than 10% hemolysis. In conclusion, the biocompatible AuNPs-scFvD2B-PEG presents promising characteristics for PC targeted therapy, with minimal protein adsorption affinity, low immunorecognition, and reduced hemolytic activity.

Solution phase growth and analysis of super-thin zigzag tin selenide nanoribbons.

Tin selenide (SnSe), a highly promising layered material, has been garnering particular interest in recent times due to its significant promise for future energy devices. Herein we report a simple solution-phase approach for growing highly crystalline layered SnSe nanoribbons. Polyvinylpyrrolidone (PVP) was used as a templating agent to selectively passivates the (100) and (001) facets of the SnSe nanoribbons resulting in the unique growth of nanoribbons along theirb-axis with a defined zigzag edge state along the sidewalls. The SnSe nanoribbons are few layers thick (∼20 layers), with mean widths of ∼40 nm, and achievable length of >1µm. Nanoribbons could be produced in relatively high quantities (>150 mg) in a single batch experiment. The PVP coating also offers some resistance to oxidation, with the removal of the PVP seen to lead to the formation of a SnSe/SnOxcore-shell structure. The use of non-toxic PVP to replace toxic amines that are typically employed for other 1D forms of SnSe is a significant advantage for sustainable and environmentally friendly applications. Heat transport properties of the SnSe nanoribbons, derived from power-dependent Raman spectroscopy, demonstrate the potential of SnSe nanoribbons as thermoelectric material.

Jumping on the Bandwagon: A Review on the Versatile Applications of Gold Nanostructures in Prostate Cancer.

Prostate cancer (PCa) has remarkably emerged as a prominent disease in the face of the male population. Conventional treatments like prostatectomy or radiation can be curative only if PCa is diagnosed at an early stage. In the field of targeted therapy, a bevy of novel therapeutic approaches have left a landmark in PCa treatment and have proven to extend survival via distinct modes of actions. Nanotherapy has started to take root and has become the hype of the century by virtue of its abundant advantages. Scientists have invested a great deal of interest in the development of nanostructures such as gold nanoparticles (AuNPs), which hold particularly great hope for PCa theranostics. In this article, we present an overview of the studies published after 1998 that involve the use of different functionalized AuNPs to treat and diagnose PCa. Special reference is given to various in vitro and in vivo methods employed to shuttle AuNPs to PCa cells. Major studies show an enhancement of either detection or treatment of PCa when compared to their non-targeted counterparts, especially when AuNPs are tagged with specific ligands, such as antibodies, tea natural extracts, folate, anisamide, receptor inhibitors, and chitosan. Future approaches of treatment are dependent on those worthy multifunctional molecules, and are dictated by their ability to achieve a more versatile cancer therapeutic approach.

Gold Nanoparticles Conjugated with Dendrigraft Poly-L-lysine and Folate-Targeted Poly(ethylene glycol) for siRNA Delivery to Prostate cancer.

Dendrigraft Poly-L-Lysine (d-PLL) coated gold nanoparticles (AuNPs) were synthesized by reducing Tetrachloroauric acid with ascorbic acid in the presence of d-PLL. AuNPs-d-PLL formed a stable colloidal solution that absorbs light at a maximum wavelength (λmax) centered at 570 nm as demonstrated by UV-visible (UV-Vis) spectroscopy. From Scanning Electron Microscopy (SEM) analysis, AuNPs-d-PLL were spherical in shape with a mean diameter of 128 ± 47 nm. Dynamic Light scattering (DLS) analysis of the colloidal solution exhibited one size distribution with a hydrodynamic diameter of about 131 nm (size distribution by intensity). Zeta potential (ξ) measurements revealed positively charged AuNPs-d-PLL with ξ about 32 mV, an indicator of high stability in an aqueous solution. The AuNPs-d-PLL was successfully modified with either thiolated poly (ethylene glycol) SH-PEG-OCH3 (Mw 5400 g mol-1) or folic acid-modified thiolated poly (ethylene glycol) SH-PEG-FA of similar molecular weight as demonstrated via DLS and Zeta potential measurements. Complexation of PEGylated AuNPs-d-PLL with siRNA was confirmed by DLS and gel electrophoresis. Finally, we analyzed the functionalization of our nanocomplexes with folic acid via targeted cellular uptake to prostate cancer cells using flow cytometry and LSM imaging. Our findings implicate the broader applicability of folate-PEGylated AuNPs in siRNA-based therapeutics against prostate cancer and perhaps other types of cancer.

D2B-Functionalized Gold Nanoparticles: Promising Vehicles for Targeted Drug Delivery to Prostate Cancer.

Despite the multitude of therapeutic agents available to treat prostate cancer (PC), there are still no effective and safe measures to treat the tumor. It remains a challenge to develop a simple approach to target PC with specific antibodies. In our study, D2B monoclonal antibodies against a prostate-specific membrane antigen (PSMA) were used. We investigated the functionalization of gold nanoparticles (AuNPs) with D2B to generate favorable physicochemical and biological properties that mediate specific binding to PC. For this purpose, AuNPs with a size of about 25 nm were synthesized in water using sodium citrate as a reducing and stabilizing agent and then coated with D2B. Major physicochemical properties of naked and D2B-coated AuNPs were investigated by ultraviolet-visible (UV-vis) spectroscopy, dynamic light scattering (DLS), and zeta potential measurements. The successful binding of D2B to AuNPs-citrate caused a 15 nm red shift in the UV-vis. This was assessed by DLS as an increase in zeta potential from ∼-45 to ∼-23 mV and in the size of AuNPs from ∼25 to ∼63 nm. Scanning electron microscopy confirmed the size shift of AuNPs, which was detected as an exterior organic layer of D2Bs surrounding each AuNP. Even at high exposure levels of the bioconjugates, PSMA-PC-3 cells exhibited minimal cytotoxicity. The specific and dose-dependent binding of AuNPs-D2B to PC-3-PSMA cells was validated by flow cytometry analysis. Our data provide effective drug delivery systems in PC theranostics.

A simple protocol to stabilize gold nanoparticles using amphiphilic block copolymers: stability studies and viable cellular uptake.

Di- and triblock non-ionic copolymers based on poly(ethylene oxide) and poly(propylene oxide) were studied for the stabilization of nanoparticles in water at high ionic strength. The effect of the molecular architecture (di- vs. triblock) of these amphiphilic copolymers was investigated by using gold nanoparticles (AuNPs) as probes for colloidal stability. The results demonstrate that both di- and triblock copolymers can provide long term stability, and that in both cases AuNPs are individually embedded within globules of polymers. However, in the case of diblock copolymers, the colloidal stability was related to the formation of micelles, in contrast with the case of triblock copolymers, which were previously shown to provide good stability even at concentrations at which micelles do not form. Quartz crystal microbalance (QCM) experiments showed that the presence of the hydrophobic block in the structure of the polymer is important to ensure quantitative adsorption upon a gold surface and to limit desorption. We demonstrate that with an appropriate choice of polymer, the polymer/AuNP hybrids can also undergo filtration and freeze-drying without noticeable aggregation, which can be very convenient for further applications. Finally, preliminary studies of the cytotoxicity effect on fibroblast cells show that the polymer/AuNP hybrids were not cytotoxic. TEM micrographs on ultrathin sections of cells after incubation with the colloidal solutions show that the nanoparticles were internalized into the cells, conserving their initial size and shape.

Chemistry Routes for Copolymer Synthesis Containing PEG for Targeting, Imaging, and Drug Delivery Purposes.

Polyethylene glycol (PEG) is one of the most frequently used polymers for coating nanocarriers to enhance their biocompatibility, hydrophilicity, stability, and biodegradability. PEG is now considered to be among the best biocompatible polymers. It offers sterical hindrance against other nanoparticles and blood components such as opsonin, preventing their macrophage phagocytosis and resulting in a prolonged circulation time in blood stream, consequently a 'stealth character' in vivo. Therefore, PEG has a very promising future for the development of current therapeutics and biomedical applications. Moreover, the vast number of molecules that PEG can conjugate with might enhance its ability to have an optimistic perspective for the future. This review will present an update on the chemistry used in the modern conjugation methods for a variety of PEG conjugates, such methods include, but are not limited to, the synthesis of targeting PEG conjugates (i.e., Peptides, Folate, Biotin, Mannose etc.), imaging PEG conjugates (i.e., Coumarin, Near Infrared dyes etc.) and delivery PEG conjugates (i.e., doxorubicin, paclitaxel, and other hydrophobic low molecular weight drugs). Furthermore, the type of nanoparticles carrying those conjugates, along with their biomedical uses, will be briefly discussed.

Bioconjugated Gold Nanoparticles Enhance siRNA Delivery in Prostate Cancer Cells.

Here we describe a simple way to create a gold nanoparticle (AuNP)-based non-viral delivery system to deliver siRNA into prostate cancer cells. Therefore, positively charged polyethylenimine (PEI)-capped AuNPs were synthesized in water and further conjugated with the targeting ligand (folic acid) for folate receptors (AuNPs-PEI-FA). The AuNPs-PEI-FA could effectively complex small interfering RNA (siRNA) through electrostatic interaction. Flow cytometry displayed that AuNPs-PEI-FA could specifically deliver siRNA into LNCaP cells, a prostate cancer cell line overexpressing prostate-specific membrane antigen (PSMA) that exhibits a hydrolase enzymatic activity with a folate substrate. In contrast, internalization of siRNA into PC-3 cells, a prostate cancer cell line not expressing PSMA or folate receptors, was not achieved using AuNPs-PEI-FA.siRNA. Following endolysosomal escape, the AuNPs-PEI-FA-.siRNA formulation resulted in significant endogenous gene silencing when compared to the nontargeted formulation, suggesting the potential of AuNPs-PEI-FA for targeted delivery of therapeutic siRNAs in the treatment of prostate cancer.

Development of anisamide-targeted PEGylated gold nanorods to deliver epirubicin for chemo-photothermal therapy in tumor-bearing mice.

BACKGROUND: Gold nanorods (AuNRs), due to the optical and electronic properties namely the surface plasma resonance, have been developed to achieve the light-mediated photothermal therapy (PTT) for cancer. However, PTT alone may suffer from inefficient tumor killing. Recently, the combination of PTT and chemotherapy has been utilized to achieve synergistic anticancer effects. METHODS: In this study, AuNRs capped with hexadecyltrimethylammonium bromide (CTAB), poly(acrylic acid) (PAA), and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of negatively charged anisamide-targeted PEGylated AuNRs (namely Au-CTAB-PAA-PEG-AA) for the combination of PTT and chemotherapy (termed as chemo-photothermal therapy [CPTT]). Epirubicin (EPI, an anthracycline drug) was efficiently loaded onto the surface of Au800-CTAB-PAA-PEG-AA via the electrostatic interaction forming Au800-CTAB-PAA-PEG-AA.EPI complex. RESULTS: The resultant complex demonstrated pH-dependent drug release, facilitated nucleus trafficking of EPI, and induced antiproliferative effects in human prostate cancer PC-3 cells. When Au800-CTAB-PAA-PEG-AA.EPI complex was further stimulated with desired laser irradiation, the synergistic outcome was evident in PC-3 xenograft mice. CONCLUSION: These results demonstrate a promising strategy for clinical application of CPTT in cancer.

Anisamide-targeted PEGylated gold nanoparticles designed to target prostate cancer mediate: Enhanced systemic exposure of siRNA, tumour growth suppression and a synergistic therapeutic response in combination with paclitaxel in mice.

Small interfering RNA (siRNA) has recently illustrated therapeutic potential for malignant disorders. However, the clinical application of siRNA-based therapeutics is significantly retarded by the paucity of successful delivery systems. Recently, multifunctional gold nanoparticles (AuNPs) as non-viral delivery carriers have shown promise for transporting chemotherapeutics, proteins/peptides, and genes. In this study, AuNPs capped with polyethylenimine (PEI) and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of positively charged anisamide-targeted PEGylated AuNPs (namely Au-PEI-PEG-AA). The anisamide-targeted AuNPs effectively complexed siRNA via electrostatic interaction, and the resultant complex (Au110-PEI-PEG5000-AA.siRNA) illustrated favourable physicochemical characteristics, including particle size, surface charge, and stability. In vitro, anisamide-targeted AuNPs selectively bound to human prostate cancer PC-3 cells, inducing efficient endosomal escape of siRNA, and effective downregulation of the RelA gene. In vivo, prolonged systemic exposure of siRNA was achieved by anisamide-targeted AuNPs resulting in significant tumour growth suppression in a PC3 xenograft mouse model without an increase in toxicity. In addition, a combination of siRNA-mediated NF-κB knockdown using anisamide-targeted AuNPs with Paclitaxel produced a synergistic therapeutic response, thus providing a promising therapeutic strategy for the treatment of prostate cancer.

Pluronics-stabilized gold nanoparticles: investigation of the structure of the polymer-particle hybrid.

Hybrid gold-polymer nanoparticles are obtained by self-assembly of amphiphilic copolymers (Pluronics) in solutions containing preformed gold nanoparticles (diameter ca. 12 nm). Dynamic light scattering, TEM, cryo-TEM, and small-angle neutron scattering experiments with contrast variation are used to characterize the structure of the gold-polymer particles. Five Pluronics (F127, F68, F88, F108, P84) with different molecular weights and hydrophilic/hydrophobic balances are investigated. Gold nanoparticles are individually embedded within globules of polymer, even under conditions for which Pluronics micelles do not form in solution. The hybrid particles are several tens of nanometers in size (larger than micelles of the corresponding Pluronics), and the size can be tuned by changing the temperature.

Gold nanoparticles enlighten the future of cancer theranostics.

Development of multifunctional nanomaterials, one of the most interesting and advanced research areas in the field of nanotechnology, is anticipated to revolutionize cancer diagnosis and treatment. Gold nanoparticles (AuNPs) are now being widely utilized in bio-imaging and phototherapy due to their tunable and highly sensitive optical and electronic properties (the surface plasmon resonance). As a new concept, termed "theranostics," multifunctional AuNPs may contain diagnostic and therapeutic functions that can be integrated into one system, thereby simultaneously facilitating diagnosis and therapy and monitoring therapeutic responses. In this review, the important properties of AuNPs relevant to diagnostic and phototherapeutic applications such as structure, shape, optics, and surface chemistry are described. Barriers for translational development of theranostic AuNPs and recent advances in the application of AuNPs for cancer diagnosis, photothermal, and photodynamic therapy are discussed.

Bioconjugated gold nanoparticles enhance cellular uptake: A proof of concept study for siRNA delivery in prostate cancer cells.

The chemistry of gold nanoparticles (AuNPs) facilitates surface modifications and thus these bioengineered NPs have been investigated as a means of delivering a variety of therapeutic cargos to treat cancer. In this study we have developed AuNPs conjugated with targeting ligands to enhance cell-specific uptake in prostate cancer cells, with a purpose of providing efficient non-viral gene delivery systems in the treatment of prostate cancer. As a consequence, two novel AuNPs were synthesised namely AuNPs-PEG-Tf (negatively charged AuNPs with the transferrin targeting ligands) and AuNPs-PEI-FA (positively charged AuNPs with the folate-receptor targeting ligands). Both bioconjugated AuNPs demonstrated low cytotoxicity in prostate cancer cells. The attachment of the targeting ligand Tf to AuNPs successfully achieved receptor-mediated cellular uptake in PC-3 cells, a prostate cancer cell line highly expressing Tf receptors. The AuNPs-PEI-FA effectively complexed small interfering RNA (siRNA) through electrostatic interaction. At the cellular level the AuNPs-PEI-FA specifically delivered siRNA into LNCaP cells, a prostate cancer cell line overexpressing prostate specific membrane antigen (PSMA, exhibits a hydrolase enzymic activity with a folate substrate). Following endolysosomal escape the AuNPs-PEI-FA.siRNA formulation produced enhanced endogenous gene silencing compared to the non-targeted formulation. Our results suggest both formulations have potential as non-viral gene delivery vectors in the treatment of prostate cancer.

Anisamide-targeted gold nanoparticles for siRNA delivery in prostate cancer - synthesis, physicochemical characterisation and in vitro evaluation.

Metastatic prostate cancer is a leading cause of cancer-related death in men and current chemotherapies are largely inadequate in terms of efficacy and toxicity. Hence improved treatments are required. The application of siRNA as a cancer therapeutic holds great promise. However, translation of siRNA into the clinic is dependent on the availability of an effective delivery system. Gold nanoparticles (AuNPs) are known to be effective and non-toxic siRNA delivery agents. In this study, a stable gold nanosphere coated with poly(ethylenimine) (PEI) was prepared to yield PEI capped AuNPs (Au-PEI). The PEI was further conjugated with the targeting ligand anisamide (AA, is known to bind to the sigma receptor overexpressed on the surface of prostate cancer cells) to produce an anisamide-targeted nanoparticle (Au-PEI-AA). The resulting untargeted and targeted nanoparticles (Au-PEI and Au-PEI-AA respectively) were positively charged and efficiently complexed siRNA. Au-PEI-AA mediated siRNA uptake into PC3 prostate cancer cells via binding to the sigma receptor. In addition, the Au-PEI-AA·siRNA complexes resulted in highly efficient knockdown of the RelA gene (∼70%) when cells were transfected in serum-free medium. In contrast, no knockdown was observed in the presence of serum, suggesting that adsorption of serum proteins inhibits the binding of the anisamide moiety to the sigma receptor. This study provides (for the first time) proof of principle that anisamide-labelled gold nanoparticles can target the sigma receptor. Further optimisation of the formulation to increase serum stability will enhance its potential to treat prostate cancer.

Evaluation of the physicochemical properties and the biocompatibility of polyethylene glycol-conjugated gold nanoparticles: A formulation strategy for siRNA delivery.

The potential of RNA interference (RNAi)-based therapeutics for cancer has received much attention; however, delivery of RNAi effectors, such as small interfering RNA (siRNA), remains an obstacle to clinical translation. Non-viral delivery vectors have been used extensively to enhance siRNA delivery. Recently, the potential of gold nanoparticles (AuNPs) for transporting drugs, proteins and genetic materials has been demonstrated. Previously, our laboratory synthesised positively charged, surfactant-free AuNPs in water by the reduction of gold (III) chloride (AuCl3) using hydroxylamine hydrochloride (NH2OH·HCl) in the presence of L-cysteine methyl ester hydrochloride (HSCH2CH(NH2)COOCH3·HCl) as a capping agent. These AuNPs, which achieve higher cell viability in comparison to cetyl trimethyl ammonium bromide (CTAB, a surfactant)-capped counterparts, have demonstrated potential for siRNA delivery. However, it is well known that systemic administration of cationic delivery systems without biological stablising moieties causes non-specific binding with negatively charged serum proteins, resulting in particle aggregation and opsonisation. Consequently, highly stable AuNPs capped with l-cysteine methyl ester hydrochloride conjugated to poly(ethylene glycol) (PEG) were synthesised in this study. PEGylation enhanced the biocompatibility of the AuNPs by reducing toxicity in a range of cell types, by inhibiting interaction with serum proteins thus avoiding aggregation, and, by providing protection against degradation by nucleases. Moreover, these PEGylated AuNPs formed nanoparticles (NPs) with siRNA (which was first compacted with protamine), and had a diameter within the nanoscale range (∼ 250 nm) and a near neutral surface charge (∼ 10 mV). In the future a bifunctional PEG chain on the AuNPs (i.e., SH-PEG-NH2, SH-PEG-COOH) will be used to facilitate conjugation of a targeting ligand to enhance cell specific uptake.

Bioconjugated iron oxide nanocubes: synthesis, functionalization, and vectorization.

A facile bottom-up approach for the synthesis of inorganic/organic bioconjugated nanoprobes based on iron oxide nanocubes as the core with a nanometric silica shell is demonstrated. Surface coating and functionalization protocols developed in this work offered good control over the shell thickness (8-40 nm) and enabled biovectorization of SiO2@Fe3O4 core-shell structures by covalent attachment of folic acid (FA) as a targeting unit for cellular uptake. The successful immobilization of folic acid was investigated both quantitatively (TGA, EA, XPS) and qualitatively (AT-IR, UV-vis, ζ-potential). Additionally, the magnetic behavior of the nanocomposites was monitored after each functionalization step. Cell viability studies confirmed low cytotoxicity of FA@SiO2@Fe3O4 conjugates, which makes them promising nanoprobes for targeted internalization by cells and their imaging.

Pegylation increases platelet biocompatibility of gold nanoparticles.

The increasing use of gold nanoparticles in medical diagnosis and treatment has raised the concern over their blood compatibility. The interactions of nanoparticles with blood components may lead to platelet aggregation and endothelial dysfunction. Therefore, medical applications of gold nanoparticles call for increased nanoparticle stability and biocompatibility. Functionalisation of nanoparticles with polythelene glycol (PEGylation) is known to modulate cell-particle interactions. Therefore, the aim of the current study was to investigate the effects of PEGylated-gold nanoparticles on human platelet function and endothelial cells in vitro. Gold nanoparticles, 15 nm in diameter, were synthesised in water using sodium citrate as a reducing and stabilising agent. Functionalised polyethylene glycol-based thiol polymers were used to coat and stabilise pre-synthesised gold nanoparticles. The interaction of gold nanoparticles-citrate and PEGylated-gold nanoparticles with human platelets was measured by Quartz Crystal Microbalance with Dissipation. Platelet-nanoparticles interaction was imaged using phase-contrast, scanning and transmission electron microscopy. The inflammatory effects of gold nanoparticles-citrate and PEGylated-gold nanoparticles in endothelial cells were measured by quantitative real time polymerase chain reaction. PEGylated-gold nanoparticles were stable under physiological conditions and PEGylated-gold nanoparticles-5400 and PEGylated-gold nanoparticles-10800 did not affect platelet aggregation as measured by Quartz Crystal Microbalance with Dissipation. In addition, PEGylated-gold nanoparticles did not induce an inflammatory response when incubated with endothelial cells. Therefore, this study shows that PEGylated-gold nanoparticles with a higher molecular weight of the polymer chain are both platelet- and endothelium-compatible making them attractive candidates for biomedical applications.

Non-solvolytic synthesis of aqueous soluble TiO2 nanoparticles and real-time dynamic measurements of the nanoparticle formation.

Highly aqueously dispersible (soluble) TiO2 nanoparticles are usually synthesized by a solution-based sol-gel (solvolysis/condensation) process, and no direct precipitation of titania has been reported. This paper proposes a new approach to synthesize stable TiO2 nanoparticles by a non-solvolytic method - direct liquid phase precipitation at room temperature. Ligand-capped TiO2 nanoparticles are more readily solubilized compared to uncapped TiO2 nanoparticles, and these capped materials show distinct optical absorbance/emission behaviors. The influence of ligands, way of reactant feeding, and post-treatment on the shape, size, crystalline structure, and surface chemistry of the TiO2 nanoparticles has been thoroughly investigated by the combined use of X-ray diffraction, transmission electron microscopy, UV-visible (UV-vis) spectroscopy, and photoluminescence (PL). It is found that all above variables have significant effects on the size, shape, and dispersivity of the final TiO2 nanoparticles. For the first time, real-time UV-vis spectroscopy and PL are used to dynamically detect the formation and growth of TiO2 nanoparticles in solution. These real-time measurements show that the precipitation process begins to nucleate after an initial inhibition period of about 1 h, thereafter a particle growth occurs and reaches the maximum point after 2 h. The synthesis reaction is essentially completed after 4 h.

The use of quartz crystal microbalance with dissipation (QCM-D) for studying nanoparticle-induced platelet aggregation.

Interactions between blood platelets and nanoparticles have both pharmacological and toxicological significance and may lead to platelet activation and aggregation. Platelet aggregation is usually studied using light aggregometer that neither mimics the conditions found in human microvasculature nor detects microaggregates. A new method for the measurement of platelet microaggregation under flow conditions using a commercially available quartz crystal microbalance with dissipation (QCM-D) has recently been developed. The aim of the current study was to investigate if QCM-D could be used for the measurement of nanoparticle-platelet interactions. Silica, polystyrene, and gold nanoparticles were tested. The interactions were also studied using light aggregometry and flow cytometry, which measured surface abundance of platelet receptors. Platelet activation was imaged using phase contrast and scanning helium ion microscopy. QCM-D was able to measure nanoparticle-induced platelet microaggregation for all nanoparticles tested at concentrations that were undetectable by light aggregometry and flow cytometry. Microaggregates were measured by changes in frequency and dissipation, and the presence of platelets on the sensor surface was confirmed and imaged by phase contrast and scanning helium ion microscopy.