Conformational-transited protein corona regulated cell-membrane penetration and induced cytotoxicity of ultrasmall Au nanoparticles

Nanoparticles (NP) in biological fluids almost invariably become coated with proteins to form protein coronas. It is the NP–protein corona rather than the bare nanoparticle that determines the nanoparticle''s bio-behavior. Here, ultrasmall gold nanoparticles (AuNPs) coated by a human serum albumin (HSA) corona were studied by Fourier transform infrared spectroscopy, denature experiments, fluorescence quenching. Moreover, the intracellular fate of AuNPs and the AuNP–HSA corona has also been investigated. The results show that HSA corona undergo a conformational transition (partial β-sheet changed to α-helicity) when they adsorb on AuNPs, which lead to an enhanced thermal stability. Importantly, we observed that the conformation-transited protein corona–AuNP complex could induce cell apoptosis. Meanwhile, for the first time, the conformation-transited HSA on the AuNPs surface are shown to disrupt living cell membranes. The results obtained here not only provide the detailed conformational behavior of HSA molecules on nanoparticles, but also reveal the structure–function relationship of protein corona, which is of utmost importance in the safe application of nanoscale objects in living organisms.

This study demonstrate that the AuNP–HSA corona could penetrate cell membranes and companied by substantial membrane disruption. However, the ultrasmall AuNPs can be internalized by cells without the destruction of cell membranes.     

Covalent immobilization of gold nanoparticles on a plastic substrate and subsequent immobilization of biomolecules

We propose a novel approach to stably immobilize gold nanoparticles (AuNPs) on a plastic substrate and demonstrate that the modified substrate is also capable of immobilizing biomolecules. To immobilize citrate-capped AuNPs, an acrylic substrate was simply dip-coated in a functional polymer solution to decorate the outermost surface with amino groups. Electrostatic interactions between AuNPs and the amino groups immobilized the AuNPs with a high density. The AuNP-modified acrylic substrate was transparent with a red tint. A heat treatment promoted the formation of amide bonds between carboxy groups on the AuNPs and amino groups on the substrate surface. These covalent bonds stabilized the immobilized AuNPs and the resulting substrate was resistant to washing with acid and thiol-containing solutions. The surface density of AuNPs was controlled by the surface density of amino groups on the substrate surface, which was in turn controlled by the dip-coating in the functional polymer solution. We attempted to immobilize functional biomolecules on the AuNPs-functionalized plastic surface by two different approaches. An enzyme (horseradish peroxidase) was successfully immobilized on the AuNPs through amide formation and 5′-thiolated DNA was also immobilized on the AuNPs through S–Au interactions. These chemistries allow for simultaneous immobilization of two different kinds of biomolecules on a plastic substrate without loss of their functional properties.

We propose a novel approach to stably immobilize gold nanoparticles (AuNPs) on a plastic substrate and demonstrate that the modified substrate is also capable of immobilizing biomolecules.     

Doxorubicin loaded ferritin nanoparticles for ferroptosis enhanced targeted killing of cancer cells

In recent years, ferroptosis has been investigated widely as a new form of cell death. Development of nanodrugs for ferroptosis induction in cancer cells may be a promising approach for cancer treatment. Here, we developed a type of nanoparticle consisting of the antitumor drug doxorubicin and exogenous ferritin. The drug loading process did not change the size of ferritin obviously. And this nanoparticle could induce the accumulation of ROS and cell ferroptosis for transferrin receptor overexpressed tumor cell, HT29. The ferroptosis process was also confirmed using inhibitors for ferroptosis. The cytotoxicity of this nanoparticle is similar to that of free DOX. This study provides a new strategy for targeting and killing transferrin receptor overexpressed tumor cells.

DOX loaded ferritin selectively induces ferroptosis enhanced killing of transferrin receptor 1 overexpressed cancer cells.     

Targeted drug release system based on pH-responsive PAA-POSS nanoparticles

An amphipathic PAA-POSS@DOX drug delivery system that responds sensitively to pH changes in the cancer microenvironment has been developed using a nanoparticle based on inorganic polyhedral oligomeric silsesquioxane (POSS). POSS was introduced to the carboxylic acid group of polyacrylic acid to which doxorubicin anticancer drug was loaded to prepare 480 ± 192 nm self-assembled nanoparticles. PAA-POSS had a high loading efficiency of over 75% and doxorubicin was quickly released to the target area responding sensitively to weakly acidic conditions. The possibility of employing PAA-POSS as a targeted drug delivery system has been confirmed by observing the death of cells of the MDA-MB-231 breast cancer line.

pH-sensitive PAA-POSS@DOX nanoparticles were synthesized and showed high loading efficiency of over 75% and doxorubicin was quickly released to the target area. The ability of PAA-POSS@DOX to kill MDA-MB-231 breast cancer cells has been demonstrated.     

Magnetic resonance imaging,gadolinium neutron capture therapy,and tumor cell detection using ultrasmall Gd2O3 nanoparticles coated with polyacrylic acid-rhodamine B as a multifunctional tumor theragnostic agent

Monodisperse and ultrasmall gadolinium oxide (Gd₂O₃) nanoparticle colloids (d_avg = 1.5 nm) (nanoparticle colloid = nanoparticle coated with hydrophilic ligand) were synthesized and their performance as a multifunctional tumor theragnostic agent was investigated. The aqueous ultrasmall nanoparticle colloidal suspension was stable and non-toxic owing to hydrophilic polyacrylic acid (PAA) coating that was partly conjugated with rhodamine B (Rho) for an additional functionalization (mole ratio of PAA : Rho = 5 : 1). First, the ultrasmall nanoparticle colloids performed well as a powerful T₁ magnetic resonance imaging (MRI) contrast agent: they exhibited a very high longitudinal water proton relaxivity (r₁) of 22.6 s⁻¹ mM⁻¹ (r₂/r₁ = 1.3, r₂ = transverse water proton relaxivity), which was ∼6 times higher than those of commercial Gd-chelates, and high positive contrast enhancements in T₁ MR images in a nude mouse after intravenous administration. Second, the ultrasmall nanoparticle colloids were applied to gadolinium neutron capture therapy (GdNCT) in vitro and exhibited a significant U87MG tumor cell death (28.1% net value) after thermal neutron beam irradiation, which was 1.75 times higher than that obtained using commercial Gadovist. Third, the ultrasmall nanoparticle colloids exhibited stronger fluorescent intensities in tumor cells than in normal cells owing to conjugated Rho, proving their pH-sensitive fluorescent tumor cell detection ability. All these results together demonstrate that ultrasmall Gd₂O₃ nanoparticle colloids are the potential multifunctional tumor theragnostic agent.

Ultrasmall Gd₂O₃ nanoparticle colloids coated with PAA and Rho-PAA were synthesized and applied to T₁ MRI, GdNCT and fluorescent tumor cell detection.     

Interaction effects on a gold nanoparticle-based colorimetric assay for antioxidant capacity evaluation of polyphenols

A gold nanoparticle (AuNP)-based colorimetric assays have been applied to evaluate the total antioxidant capacities (TAC) of various food samples, while the potential endogenous polyphenol interaction effects on the AuNP assays are less explored. In this work, 12 representative polyphenols were strategically selected, and their corresponding AuNPs were synthesized and characterized by UV-Vis spectroscopy and transmission electron microscopy, which conformed the formation of AuNPs. Then, the TAC of the polyphenols, alone and in their equimolar binary or ternary combinations, were estimated and their synergistic effects were evaluated. In addition, the matrix effects of endogenous components from 6 kinds of foods on the recovery of the TAC estimation of gallic acid and rutin were evaluated. Markedly stronger interaction effects and matrix effects were observed in the AuNP assay than in conventionally well-established methods, indicating that the validation and application of the AuNP assay for TAC evaluation should be fully studied and explored.

Interaction effects of endogenous polyphenols remarkably influenced the performance of gold nanoparticle-based colorimetric assay for antioxidant capacity evaluation.     

Active targeting drug-gold nanorod hybrid nanoparticles for amplifying photoacoustic signal and enhancing anticancer efficacy

The development of theranostic nanomaterials with limited side effects and increased therapeutic efficacy is a promising approach for cancer imaging and therapy. In the present study, the development of a multifunctional metal–organic hybrid nanoparticle (NP) with enhanced photoacoustic (PA) imaging performance able to be actively uptaken by cancer cells for synergistic chemo-photothermal cancer therapy was reported. The theranostic NP was composed through the coordination effect between an ultrasmall gold nanorod (AuNR), a thick coating layer of the organic near-infrared dye IR780, and the anticancer drug doxorubicin (DOX), named AuNR@IR780/DOX-RGD-PEG. In addition, the theranostic NP surface was conjugated with targeting ligand RGD and a protective PEG shell, where the PEG played a role in concealing or exposing the RGD for specific targeting of the NPs to the cancer cells. The theranostic NP demonstrated a greatly enhanced PA imaging signal compared to AuNR or IR780, due to the fact that the electromagnetic field of the AuNR increased the light absorption efficiency of the IR780 coating based on the theoretical simulation results. Furthermore, the “Trojan-horse” active targeting strategy not only increased the uptake of NPs by tumor cells, but also decreased the non-specific uptake by healthy cells, thus limiting the side effects. This study developed a smart theranostic NP for enhanced cancer PA imaging and specific cancer therapy.

We developed a multifunctional metal–organic hybrid nanoparticle with enhanced photoacoustic imaging performance and specific chemo-photothermal cancer therapy.     

AuNP and ssDNA capped mesoporous silica nanoparticles for laser controlled drug release

In order to improve drug efficacy, and reduce drug toxicity and side effects, a novel drug controlled release system was developed based on mesoporous silica nanoparticles (MSNs) with gold nanoparticles (AuNPs) acting as pore caps and short single-stranded DNA (ssDNA) oligomers as the linker. The synthesised composites were characterized by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), zeta potential measurement, transmission electron microscopy (TEM) and UV-vis spectroscopy. The anticancer drug doxorubicin (Dox) was applied as a model drug to investigate the 808 nm near infrared (NIR) laser-controlled drug release behavior at different pH by fluorescence measurements. The investigation results demonstrate that this nanocarrier could achieve drug controlled release by external near-infrared (NIR) laser stimulation, which is expected to be applied in cancer therapy.

Gold nanoparticles were linked to the surface of mesoporous silica through a polyA oligonucleotide and infrared stimulation controlled drug release.     

Spectroscopic characterization of the warfarin drug-binding site of folded and unfolded human serum albumin anchored on gold nanoparticles: effect of bioconjugation on the loading capacity

Protein-conjugated gold nanoparticles (AuNPs) have recently shown promising applications in medicine, owing to their inertness and biocompatibility. Herein, we studied the spectroscopy of 25 nm diameter AuNPs, coated with human serum albumin (HSA) as a model drug carrier. The morphology and coating of the AuNPs were examined using transmission electron microscopy and dynamic light scattering. Resonance energy transfer from the sole tryptophan of HSA (Trp214) to the AuNPs indicates a single layer of protein coverage. Using fluorescein (FL) to probe the warfarin drug-binding site in HSA revealed an increase in the HSA–FL binding by ∼4.5 times when HSA is anchored on the nanoparticle surface, indicating a rise in the loading capacity. Femtosecond transient absorption measurements of the surface plasmonic resonance band of the AuNPs show three ultrafast dynamics that are involved in the relaxation process. The three decay components were assigned to the electron–electron (∼400 fs), electron–phonon (∼2.0 ps) and phonon–phonon (200–250 ps) interactions. These dynamics were not changed upon coating the AuNPs with HSA which indicates the chemical and physical stability of the AuNPs upon bioconjugation. Chemical unfolding of the warfarin binding site with guanidine hydrochloride (GdnHCl) was studied by measuring the spectral shift in the Trp214 fluorescence and the appearance of the Tyr fluorescence. Unfolding was shown to start at [GdnHCl] ≥ 2.0 M and is complete at [GdnHCl] = 6.0 M. HSA anchored onto the nanoparticle surface shows more resistance to the unfolding effect which is attributed to the stability of the native form of HSA on the nanoparticle surface. On the other hand, upon complete unfolding, a larger red shift in the Trp214 fluorescence was observed for the HSA–AuNP complex. This observation indicates that, upon unfolding, the HSA molecule is still anchored on the AuNP surface in which subdomain IIA is facing the outer water molecules in the bulk solution as well as the hydration shell rather than the core of the nanoparticle. The current study is important for a better understanding of the physical and dynamical properties of protein-coated metal nanoparticles, which is expected to help in optimizing their properties for critical applications in nanomedicine.

This work investigates the steady-state and ultrafast spectroscopy of bioconjugated gold nanoparticles and the implications on the protein binding activity and drug-loading capacity.     

A thio-β-cyclodextrin functionalized graphene/gold nanoparticle electrochemical sensor: a study of the size effect of the gold nanoparticles and the determination of tetrabromobisphenol A

In this study, a novel tetrabromobisphenol A (TBBPA) sensor was fabricated based on a CTAB-capped gold nanoparticle (AuNPs)-thio-β-cyclodextrin (SH-β-CD)/graphene oxide modified glassy carbon electrode (GCE). The peak current of TBBPA was dramatically enhanced by the AuNPs with a diameter of 6.2 nm on the modified electrodes compared with the other sized particles (10.1 or 16.1 nm). To further improve the electrochemical performance of the modified electrode, the influence of pH of the buffer solution and the accumulation time on the determination were investigated. The optimum pH and accumulation time were 7.0 and 180 s, respectively. The developed sensor exhibited good reproducibility, and excellent sensitivity and selectivity, showing a low detection limit (1.2 × 10⁻⁹ mol L⁻¹) and a linear range from 1.5 × 10⁻⁸ to 7 × 10⁻⁶ mol L⁻¹. In addition, a possible oxidization mechanism of TBBPA was also discussed. Finally, this sensor was successfully applied to detect TBBPA in water samples, and the results were consistent with those acquired by high-performance liquid chromatography.

In this study, a novel tetrabromobisphenol A (TBBPA) sensor was fabricated based on a CTAB-capped gold nanoparticle (AuNP)-thio-β-cyclodextrin (SH-β-CD)/graphene oxide modified glassy carbon electrode (GCE).     

Microfluidic chip for droplet-based AuNP synthesis with dielectric barrier discharge plasma and on-chip mercury ion detection

This study presents a novel microfluidic chip that can achieve on-demand gold nanoparticle (AuNP) synthesis using atmospheric pressure helium plasma and on-site mercury ion detection. Instead of using conventional chemical reaction methods, this chip uses helium plasma as the reducing agent to reduce gold ions and to synthesize AuNP, such that there is no residual reducing agent in the solution after removing the external electric field for plasma generation. The plasma discharge, gas–liquid separation, liquid collection and mercury ion detection can be achieved by this proposed microfluidic chip. The synthesized gold nanoparticles are further functionalized by 3-mercaptopropionic acid (3-MPA) for mercury ion detection. The 3-MPA-capped gold nanoparticles aggregate and result in a colour change of the solution due to the existence of Hg²⁺. The absorption spectra of the solution shifts from red to blue due to the cluster aggregation. The concentration of Hg²⁺ can be quantitatively determined by UV-Vis spectrometry, and the limit of detection was found to be 10⁻⁶ M (0.2 ppm). This developed integrated microfluidic device provides a simple and on-demand method for synthesis of AuNPs and Hg²⁺ detection in a single chip.

This study presents a novel microfluidic chip that can achieve on-demand gold nanoparticle (AuNP) synthesis using atmospheric pressure helium plasma and on-site mercury ion detection.     

Folic acid and deoxycholic acid derivative modified Fe3O4 nanoparticles for efficient pH-dependent drug release and multi-targeting against liver cancer cells

The novel nano-drug carrier (FDCA-FA-MNPs) was constructed by grafting formyl deoxycholic acid (FDCA) and folic acid (FA) on the surface of Fe₃O₄ magnetic nanoparticles (MNPs), possessing the advantages of superparamagnetism, good stability, low cytotoxicity and good blood compatibility. The hydrophobic anti-cancer drug doxorubicin hydrochloride (DOX) was successfully loaded onto FDCA-FA-MNPs through supramolecular interactions (hydrogen bond between FDCA and drug and hydrophobic interaction and π–π stacking between drug and drug). The drug loading amount and drug loading capacity were 509.1 mg g⁻¹ and 33.73 wt%, respectively. In addition, drug release had a pH responsive and controllable release performance, the release rate at pH 5.3 (45.6%) was four times that at pH 7.4 (11.5%), and the tumor microenvironment was favorable for drug release. More importantly, the novel nano-drug carrier combined the hepatocellular targeting of FDCA, the cancer cell targeting of FA, and the magnetic targeting of Fe₃O₄, showing excellent cancer-killing efficiency (78%) in vitro. Therefore, the nano-drug carrier synthesized in this paper has potential practical application value in the targeted therapy of liver cancer.

A nano-drug carrier, FDCA-FA-MNPs was constructed by modifying Fe₃O₄ magnetic nanoparticles (MNPs) with formyl deoxycholic acid (FDCA) and folic acid (FA) with double-targeting, pH-triggered drug release and excellent tumor cell killing efficiency.     

Bifunctional folic-conjugated aspartic-modified Fe3O4 nanocarriers for efficient targeted anticancer drug delivery

Functionalization of nanocarriers has been considered the most promising way of ensuring an accurate and targeted drug delivery system. This study reports the synthesis of bifunctional folic-conjugated aspartic-modified Fe₃O₄ nanocarriers with an excellent ability to deliver doxorubicin (DOX), an anticancer drug, into the intercellular matrix. Here, the presence of amine and carboxylate groups enables aspartic acid (AA) to be used as an efficient anchoring molecule for the conjugation of folic acid (FA) (EDC–NHS coupling) and DOX (electrostatic interaction). Based on the results, surface functionalization showed little effect on the physicochemical properties of the nanoparticles but significantly influenced both the loading and release efficiency of DOX. This is primarily caused by the steric hindrance effect due to large and bulky FA molecules. Furthermore, in vitro MTT assay of B16–F1 cell lines revealed that FA conjugation was responsible for a significant increase in the cytotoxicity of DOX-loaded nanocarriers, which was also found to be proportional to AA concentration. This high cytotoxicity resulted from an efficient cellular uptake induced by the over-expressed folate receptors and fast pH triggered DOX release inside the target cell. Here, the lowest IC₅₀ value of DOX-loaded nanocarriers was achieved at 2.814 ± 0.449 μg mL⁻¹. Besides, further investigation also showed that the drug-loaded nanocarriers exhibited less or no toxicity against normal cells.

Aspartic acid was used as an anchoring molecule for the conjugation of folic acid and doxorubicin to Fe₃O₄ nanoparticles. The as-prepared bifunctional folic-conjugated aspartic-modified Fe₃O₄ nanocarrier was shown to be as an efficient targeted anticancer drug delivery.     

Synthesis of graphene quantum dot-stabilized gold nanoparticles and their application

Herein, we report an in situ synthesis of graphene quantum dots (GQDs), which have been synthesized from only starch and water and stabilize AuNPs in water. The construction of six gold nanocomposites, i.e. AuNPs 1–6, with sizes ranging from 13.4 nm to 32.6 nm, was accomplished by only mixing the GQDs and chloroauric acid in different amounts without any additional reductants and surfactants. HRTEM has confirmed that the AuNPs have been stabilized by the GQDs, and a core/shell AuNPs@GQD structure has formed. In addition, the as-synthesized AuNPs show excellent catalytic performance in the reduction of 4-nitrophenol, a pertinacious pollutant occurring in industrial wastewater.

Herein, we report an in situ synthesis of graphene quantum dots (GQDs), which have been synthesized from only starch and water and stabilize AuNPs in water.     

Molecular basis of transport of surface functionalised gold nanoparticles to pulmonary surfactant

Ligands like alkanethiol (e.g. dodecanethiol, hexadecanethiol, etc.) and polymers (e.g. poly(vinyl pyrrolidone), polyethylene glycol-thiol) capped to the gold nanoparticles (AuNPs) are widely used in biomedical field as drug carriers and as promising materials for probing and manipulating cellular processes. Ligand functionalised AuNPs are known to interact with the pulmonary surfactant (PS) monolayer once reaching the alveolar region. Therefore, it is crucial to understand the interaction between AuNPs and PS monolayers. Using coarse-grained molecular dynamics simulations, the effect of ligand density, and ligand length have been studied for two classes of ligands on a PS model monolayer consisting of DPPC, POPG, cholesterol and SP-B (mini-peptide). The ligands considered in this study are alkanethiol and polyethylene glycol (PEG) thiol as examples of hydrophobic and hydrophilic ligands, respectively. It was observed that the interaction between AuNPs and PS changes the biophysical properties of PS monolayer in compressed and expanded states. The AuNPs with hydrophilic ligand, can penetrate through the monolayer more easily, while the AuNPs with hydrophobic ligand are embedded in the monolayer and participated in deforming the monolayer structure particularly the monolayer in the compressed state. The bare AuNPs hinder to lower the monolayer surface tension value at the interface, however introducing ligand to the bare AuNPs or increasing the ligand length and density have an impact of lowering of monolayer surface tension to a minor extent. The simulation results guide the design of ligand protected NPs as drug carriers and can identify the nanoparticles'' potential side effects on lung surfactant.

Molecular-level observations of the behavior of ligand functionalised gold nanoparticles with a lipid monolayers.     

A novel multimodal nanoplatform for targeting tumor necrosis

Peri-necrotic tumor regions have been found to be a source of cancer stem cells (CSC), important in tumor recurrence. Necrotic and peri-necrotic tumor zones have poor vascular supply, limiting effective exposure to systemically administered therapeutics. Therefore, there is a critical need to develop agents that can effectively target these relatively protected tumor areas. We have developed a multi-property nanoplatform with necrosis avidity, fluorescence imaging and X-ray tracking capabilities to evaluate its feasibility for therapeutic drug delivery. The developed nanoparticle consists of three elements: poly(ethylene glycol)-block-poly(ε-caprolactone) as the biodegradable carrier; hypericin as a natural compound with fluorescence and necrosis avidity; and gold nanoparticles for X-ray tracking. This reproducible nanoparticle has a hydrodynamic size of 103.9 ± 1.7 nm with a uniform spherical morphology (polydispersity index = 0.12). The nanoparticle shows safety with systemic administration and a stable 30 day profile. Intravenous nanoparticle injection into a subcutaneous tumor-bearing mouse and intra-arterial nanoparticle injection into rabbits bearing VX2 orthotopic liver tumors resulted in fluorescence and X-ray attenuation within the tumors. In addition, ex vivo and histological analysis confirmed the accumulation of hypericin and gold in areas of necrosis and peri-necrosis. This nanoplatform, therefore, has the potential to enhance putative therapeutic drug delivery to necrotic and peri-necrotic areas, and may also have an application for monitoring early response to anti-tumor therapies.

Au-Hyp-NP developed by encapsulation of gold and hypericin into PEG-PCL nanoplatform for fluorescence and X-ray tracking with tumor necrosis targeting.     

Interactions of neutral gold nanoparticles with DPPC and POPC lipid bilayers: simulation and experiment

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.

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.     

Roles of chitosan in synthesis,antibacterial and anti-biofilm properties of bionano silver and gold

Antibiotic-resistance and bacterial bioburden on wound surfaces are the significant challenges to wound healing. Silver and gold nanoparticles (are termed as AgNPs and AuNPs) have been investigated as alternative antimicrobial agents to combat antibiotic-resistant bacterial infections owing to their antibacterial and anti-biofilm activities. Chitosan (CS) has largely been used in nanoparticle synthesis as a stabilizing or capping agent. In this study, AgNPs and AuNPs were synthesized using different concentrations of aqueous extract of tiger milk mushroom (Lignosus rhinocerotis) (WETMM) and CS as reducing and stabilizing agent, respectively. Particle size and morphology of both were determined by dynamic light scattering (DLS) method and transmission electron microscopic analysis (TEM). FTIR analysis was conducted to determine the interactions between nanoparticle precursors. The observed peaks at 450 nm and 534–565 nm using a spectrophotometer were corresponded to the surface Plasmon resonance of AgNPs and AuNPs respectively, indicating the formation of respective nanoparticles. FTIR analysis confirmed the role of WETMM as a reducing agent and CS as a stabilizer of AgNPs and AuNPs. Faster formation of nanoparticles was observed besides an increase in particle size when higher CS concentrations were used. TEM micrographs revealed the spherical shape of most nanoparticles with particle sizes in the range of 4 to 58 nm and 18 to 28 nm for AgNPs and AuNPs, respectively. Both nanoparticles exhibited antimicrobial activity against Gram-positive and -negative bacteria, with AgNPs showing a superior antibacterial efficacy than AuNPs. Both microbroth dilution and agar well diffusion assays indicated that CS was an important component to facilitate antibacterial activity for AuNPs. Contrarily, CS stabilization did not enhance the antibacterial efficacy of AgNPs. CS-stabilized AgNPs and AuNPs achieved biofilm inhibition of 53.21% and 79.39% for Pseudomonas aeruginosa and 48.71% and 48.16% for Staphylococcus aureus, respectively. Similarly, CS stabilization enhanced the anti-biofilm activity of AuNPs but no such effect was seen for AgNPs. In conclusion, CS-stabilized AgNPs and AuNPs possess both antimicrobial and anti-biofilm activities. However, CS acted differently when combined with AgNPs and AuNPs, needing further investigation and optimization to improve the antimicrobial activity of both nanoparticles.

Biosynthesis of silver and gold nanoparticles using extract of tiger milk mushroom and stabilized by chitosan were effective at inhibiting biofilm formation and growth of Pseudomonas aeruginosa and Staphylococcus aureus, common biofilm-forming pathogens on wound surfaces.     

Analysis of gold nanospheres,nano ellipsoids,nanorods, and effect of core–shell structures for hyperthermia treatment

Hyperthermia (HT) is a technique for treating malignancies by raising the temperature of the defected tissues. This technique has been used as a treatment to raise tumor area temperatures between 42 °C to 48 °C. Hyperthermia penetrates deeper malignant cells by heating the region of interest when magnetic nanoparticles (MNPs) are exposed to an externally induced magnetic field of the incident wave. In this work, numerical analysis was used to examine the temporal and spatial temperature distributions within a tumor. The temperature field was analyzed using the mass transfer and diffusion theories in the interstitial tissue. A bio-heating module in COMSOL Multi-Physics was used for different types of gold nanoparticles (AuNPs) including nanorods, nanospheres, and nano-ellipsoids with different shapes. The objective of this study is to analyze the use of AuNPs for hyperthermia. The results show that AuNPs achieve a maximum temperature for Au nanorods as compared to nano ellipsoids and nanospheres. The Au NPs achieve thermal equilibrium after 0.5 μs and are effective for hyperthermia treatment. The results describe the effect of nanoparticle shape and surface coating on thermal absorption around the nanoparticle in hyperthermia. The significance of Au NPs for hyperthermia is explained. It is expected that this study will be helpful in the future for hyperthermia treatment.

Hyperthermia (HT) is a technique for treating malignancies by raising the temperature of the defected tissues.     

Shape-dependent adjuvanticity of nanoparticle-conjugated RNA adjuvants for intranasal inactivated influenza vaccines

Intranasal inactivated influenza vaccines can elicit mucosal immune responses that protect against virus infection. For the development of intranasal inactivated influenza vaccines, effective adjuvants inducing minimal adverse reactions are required. Generally, however, lower toxicity adjuvants have lower adjuvanticity. In this research, we fabricated nanoparticle-based adjuvants to enhance its adjuvanticity. Herein, we focused on low-molecular-weight polyinosinic-polycytidylic acid, referred to as uPIC(40:400), as a weak and less toxic RNA adjuvant. We conjugated uPIC(40:400) with different shaped gold nanoparticles (AuNPs) electrostatically. Conjugation with gold nanorods, but not spherical AuNPs, markedly enhanced the adjuvanticity of uPIC(40:400), leading to the suppression of viral infection in mice. Notably, conjugation with gold nanorods did not increase the inflammatory cytokine production in dendritic cells. These data indicated that gold nanorods can provide a good platform for enhancing the weak adjuvanticity of uPIC(40:400) while maintaining low inflammatory cytokine production toward the development of intranasal inactivated influenza vaccines.

Conjugation with gold nanorods enhanced the adjuvanticity of RNA adjuvant for intranasal inactivated influenza vaccines, providing efficient protection against infection in mice.