Charge Effect of Mercaptobenzimidazole-Modified Ultrasmall Gold-Nanoparticles against Drug-Resistant Bacteria.

The threat of bacterial infections, especially drug-resistant strains, to human health necessitates the development of high-efficient, broad-spectrum and nonantibiotic nanodisinfectant. However, the effect of interfacial charge on the antibacterial properties of nanodisinfectant remains a mystery, which greatly limits the development of highly antibacterial active nanodisinfectant. Herein, we developed three types of ultrasmall (d < 3 nm) gold-nanoparticles (AuNPs) modified with 5-carboxylic(C)/methoxy(M)amino(A)/-2-mercaptobenzimidazole (C/M/A MB) to investigate their interfacial charge on antibacterial performance. Our results showed that both the electropositive AMB-AuNPs and electronegative CMB-AuNPs exhibited no antibacterial activity against both Gram-positive (G+) and Gram-negative (G-) bacteria. However, the electroneutral MMB-AuNPs exhibited unique antibacterial performance against both G+ and G- bacteria, even against methicillin-resistant Staphylococcus aureus (MRSA). Mechanistic investigation revealed a multipathway synergistic bacteriostatic mechanism involving MMB-AuNPs inducing damage to bacterial cell membranes, disruption of membrane potential and downregulation of ATP levels, ultimately leading to bacterial demise. Furthermore, two additional electroneutral AuNPs modified with 5-methyl-2-mercaptobenzimidazole (mMB-AuNPs) and 5-ethoxy-2-mercaptobenzimidazole (EMB-AuNPs) also demonstrated commendable antibacterial efficacy against E. coli, S. aureus, and MRSA; however, their performance was comparatively inferior to that of MMB-AuNPs. This work provides valuable insights for the development of high-performance antibacterial nanomaterials.

Targeted photodynamic therapy technique of Janus nanoparticles on breast cancer.

Spherical gold/polyacrylic acid (Au/PAA) polymer-inorganic Janus nanoparticles (JNPs) with simultaneous therapeutic and targeting functions were fabricated. The obtained Au/PAA JNPs were further selectively functionalized with folic acid (FA) and thiol PEG amine (SH-PEG-NH2) on Au sides to provide superior biocompatibility and active targeting, while the other PAA sides were loaded with 5-aminolevulinic acid (5-ALA) to serve as a photosensitizer (PS) for photodynamic therapeutic (PDT) effects on MCF-7 cancer cells. The PS loading of 5-ALA was found to be 83% with an average hydrodynamic size and z-potential of 146 ± 0.8 nm and -6.40 mV respectively for FA-Au/PAA-ALA JNPs. The in vitro PDT study of the JNPs on MCF-7 breast cancer cells under 636 nm laser irradiation indicated the cell viability of 24.7% ± 0.5 for FA-Au/PAA-ALA JNPs at the IC50 value of 0.125 mM. In this regard, the actively targeted FA-Au/PAA-ALA JNPs treatment holds great potential for tumour therapy with high cancer cell-killing efficacy.

Facile synthesis of silver and gold nanoparticles using mangrove (Avicennia marina) leaves extract and its cytotoxicity and larvicidal activity.

The field of bio-fabricated noble metallic nanoparticles (NPs) has gained significant attention in applied research due to their eco-friendly and biocompatible nature. This study focuses on employing a green synthesis method to produce silver and gold nanoparticles (bio-fabricated) using a Mangrove plant extract and assessing their insecticidal and growth-inhibitory effects for environmentally friendly pest control. The resulting NPs underwent comprehensive characterization through various spectroscopy techniques. The morphology of both silver and gold mediated nanoparticles of Avicennia marina leaf extract displayed a spherical shape, with average sizes measuring around 70-80 nm and 95-100 nm, respectively. Regarding cytotoxicity, the inhibitory effects of silver nanoparticles were less than that observed by the extract alone while gold nanoparticles showed stronger cell growth inhibitory effects on splenic cells. The hepatic toxicity of silver and gold nanoparticles showed significant toxic effects as compared to A. marina extract alone. Notably, as prepared silver nanoparticles exhibited substantial larvicidal toxicity as compared to gold nanoparticles, when tested against fourth instar Culex pipiens larvae. These biocompatible silver and gold nanoparticles prepared from A. marina leaf extract hold promise for future applications as larvicides to effectively control mosquito species.

Synergistic activity of gold nanoparticles with amphotericin B on persister cells of Candida tropicalis biofilms.

AIM: The antifungal activity was studied on sessile and persister cells (PCs) of Candida tropicalis biofilms of gold nanoparticles (AuNPs) stabilized with cetyltrimethylammonium bromide (CTAB-AuNPs) and those conjugated with cysteine, in combination with Amphotericin B (AmB). MATERIALS/METHODS: The PC model was used and synergistic activity was tested by the checkerboard assay. Biofilms were studied by crystal violet and scanning electron microscopy. RESULTS/CONCLUSIONS: After the combination of both AuNPs and AmB the biofilm biomass was reduced, with significant differences in architecture being observed with a reduced biofilm matrix. In addition, the CTAB-AuNPs-AmB combination significantly reduced PCs. Understanding how these AuNPs aid in the fight against biofilms and the development of new approaches to eradicate PCs has relevance for chronic infection treatment.

Phytic Acid-Promoted Deposition of Gold Nanoparticles with Grafted Cationic Polymer Brushes for the Construction of Synergistic Contact-Killing and Photothermal Bactericidal Coatings.

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs-g-PDM). The Au NPs-g-PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs-g-PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.

Gold nanoparticles exhibit anti-osteoarthritic effects via modulating interaction of the "microbiota-gut-joint" axis.

Osteoarthritis (OA) is a common degenerative joint disease that can cause severe pain, motor dysfunction, and even disability. A growing body of research indicates that gut microbiota and their associated metabolites are key players in maintaining bone health and in the progression of OA. Short-chain fatty acids (SCFAs) are a series of active metabolites that widely participate in bone homeostasis. Gold nanoparticles (GNPs) with outstanding anti-bacterial and anti-inflammatory properties, have been demonstrated to ameliorate excessive bone loss during the progression of osteoporosis (OP) and rheumatoid arthritis (RA). However, the protective effects of GNPs on OA progression are not clear. Here, we observed that GNPs significantly alleviated anterior cruciate ligament transection (ACLT)-induced OA in a gut microbiota-dependent manner. 16S rDNA gene sequencing showed that GNPs changed gut microbial diversity and structure, which manifested as an increase in the abundance of Akkermansia and Lactobacillus. Additionally, GNPs increased levels of SCFAs (such as butyric acid), which could have improved bone destruction by reducing the inflammatory response. Notably, GNPs modulated the dynamic balance of M1/M2 macrophages, and increased the serum levels of anti-inflammatory cytokines such as IL-10. To sum up, our study indicated that GNPs exhibited anti-osteoarthritis effects via modulating the interaction of "microbiota-gut-joint" axis, which might provide promising therapeutic strategies for OA.

Induction of autophagy-dependent and caspase- and microtubule-acetylation-independent cell death by phytochemical-stabilized gold nanopolygons in colorectal adenocarcinoma cells.

Collective functionalization of the phytochemicals of medicinal herbs on nanoparticles is emerging as a potential cancer therapeutic strategy. This study presents the facile synthesis of surface-functionalized gold nanoparticles using Bacopa monnieri (Brahmi; Bm) phytochemicals and their therapeutically relevant mechanism of action in the colorectal cancer cell line, HT29. The nanoparticles were characterized using UV-visible spectroscopy, TEM-EDAX, zeta potential analysis, TGA, FTIR and 1H NMR spectroscopy, and HR-LC-MS. The particles (Bm-GNPs) were of polygonal shape and were stable against aggregation. They entered the target cells and inhibited the viability and clonogenicity of the cells with eight times more antiproliferative efficacy (25 ± 1.5 µg mL-1) than Bm extract (Bm-EX). In vitro studies revealed that Bm-GNPs bind tubulin (a protein crucial in cell division and a target of anticancer drugs) and disrupt its helical structure without grossly altering its tertiary conformation. Like other antitubulin agents, Bm-GNPs induced G2/M arrest and ultimately killed the cells, as confirmed using flow cytometry analyses. ZVAD-FMK-mediated global pan-caspase inhibition and the apparent absence of cleaved caspase-3 in treated cells indicated that the death did not involve the classic apoptosis pathway. Cellular ultrastructure analyses, western immunoblots, and in situ immunofluorescence visualization of cellular microtubules revealed microtubule-acetylation-independent induction of autophagy as the facilitator of cell death. Together, the data indicate strong antiproliferative efficacy and a possible mechanism of action for these designer nanoparticles. Bm-GNPs, therefore, merit further investigations, including preclinical evaluations, for their therapeutic potential as inducers of non-apoptotic cell death.

Effect of the Photoreduction Process on the Self-Cleaning and Antibacterial Activity of Au-Doped TiO2 Colloids on Cotton Fabric.

This study aims at understanding the effect of the photoreduction process during the synthesis of gold (Au)-doped TiO2 colloids on the conferred functionalities on cotton fabrics. TiO2/Au and TiO2/Au/SiO2 colloids were synthesized through the sol-gel method with and without undergoing the photoreduction step based on different molar ratios of Au:Ti (0.001 and 0.01) and TiO2/SiO2 (1:1 and 1:2.3). The colloids were applied to cotton fabrics, and the obtained photocatalytic self-cleaning, wet photocatalytic activity, UV protection, and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria were investigated. The obtained results demonstrated that the photoreduction of Au weakened the self-cleaning effect and reduced the photocatalytic activity of coated fabrics. Also, an excess amount of Au deteriorated the photocatalytic activity under both UV and visible light. The most efficient self-cleaning effect was obtained on fabrics coated with a ternary TiO2/Au/SiO2 colloid containing ionic Au, where it decomposed coffee and red-wine stains after 3 h of illumination. Adding silica (SiO2) made the fabrics superhydrophilic and led to greater methylene blue (MB) dye adsorption, a faster dye degradation pace, and more efficient stain removal. Moreover, the photoreduction process affected the size of Au nanoparticles (NPs), weakened the antibacterial activity of fabrics against both types of tested bacteria, and modestly increased the UV protection. In general, the photoactivity of Au-doped colloids was influenced by the synthesis method, the ionic and metallic states of the Au dopant, the concentration of the Au dopant, and the presence and concentration of silica.

Anticancer photodynamic activities of triphenylphosphine-labelled phthalocyanines and their bovine serum albumin-gold nanoparticles- complexes on melanoma A375 cell lines in vitro.

This work reports on the synthesis of triphenylphosphine-labelled cationic phthalocyanines (Pc) complexed with bovine serum albumin (BSA) and gold nanoparticles (Au NPs). This nano-complex (Pc-BSA-Au) is studied for its photodynamic therapy (PDT) activity compared to the non-complexed Pc counterpart. The photochemical properties and in vitro PDT efficacies of the Pc and the nano-complex were determined and are compared herein. The singlet oxygen (1O2) yields of the Pcs were determined and are reported in DMF. A singlet oxygen quantum yield of 0.47 was obtained for the Pcs. The PDT efficacies of the complexes were thereafter determined using malignant melanoma A375 cancer cell line in vitro. An increase in the cell toxicity was observed for cells treated with Pc-BSA-Au compared to those treated with the Pc alone. The cell survival percentages were 23.1% for cells treated with Pc-BSA-Au and 48.7% for those treated with Pc alone under PDT treatments.

Chemo-photothermal therapy of chitosan/gold nanorod clusters for antibacterial treatment against the infection of planktonic and biofilm MRSA.

Bacterial infections trigger inflammation and impede the closure of skin wounds. The misuse of antibiotics exacerbates skin infections by generating multidrug-resistant bacteria. In this study, we developed chemo-photothermal therapy (chemo-PTT) based on near-infrared (NIR)-irradiated chitosan/gold nanorod (GNR) clusters as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents. The nanocomposites exhibited an average size of 223 nm with a surface charge of 36 mV. These plasmonic nanocomposites demonstrated on-demand and rapid hyperthermal action under NIR. The combined effect of positive charge and PTT by NIR-irradiated nanocomposites resulted in a remarkable inhibition rate of 96 % against planktonic MRSA, indicating a synergistic activity compared to chitosan nanoparticles or GNR alone. The nanocomposites easily penetrated the biofilm matrix. The combination of chemical and photothermal treatments by NIR-stimulated clusters significantly damaged the biofilm structure, eradicating MRSA inside the biomass. NIR-irradiated chitosan/GNR clusters increased the skin temperature of mice by 13 °C. The plasmonic nanocomposites induced negligible skin irritation in vivo. In summary, this novel nanosystem demonstrated potent antibacterial effects against planktonic and biofilm MRSA, showcasing the possible efficacy in treating skin infections.

PDADMAC/Alginate-Coated Gold Nanorod For Eradication of Staphylococcus Aureus Biofilms.

Introduction: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections. Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV-Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied. Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 µM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy. Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.

Bioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evoked a worldwide pandemic. As the emergence of variants has hampered the neutralization capacity of currently available vaccines, developing effective antiviral therapeutics against SARS-CoV-2 and its variants becomes a significant challenge. The main protease (Mpro) of SARS-CoV-2 has received increased attention as an attractive pharmaceutical target because of its pivotal role in viral replication and proliferation. Here, we generated a de novo Mpro-inhibitor screening platform to evaluate the efficacies of Mpro inhibitors based on Mpro cleavage site-embedded amyloid peptide (MCAP)-coated gold nanoparticles (MCAP-AuNPs). We fabricated MCAPs comprising an amyloid-forming sequence and Mpro-cleavage sequence, mimicking in vivo viral replication process mediated by Mpro. By measuring the proteolytic activity of Mpro and the inhibitory efficacies of various drugs, we confirmed that the MCAP-AuNP-based platform was suitable for rapid screening potential of Mpro inhibitors. These results demonstrated that our MCAP-AuNP-based platform has great potential for discovering Mpro inhibitors and may accelerate the development of therapeutics against COVID-19.

Ameliorated Skin Inflammation through the Synergistic Effect of Gold Nanorod-Dexamethasone and Photothermal Therapy.

Psoriasis, a prevalent chronic inflammatory skin ailment affecting approximately 2-3% of the global population, is characterized by persistent symptoms. Dexamethasone, a primary corticosteroid for treating psoriasis, demonstrates notable efficacy; however, its limited skin permeation results in documented adverse effects. To address this, the presented study employed a novel strategy to conjugate gold nanorod and dexamethasone and evaluate their potential for mitigating psoriatic inflammation using an imiquimod-induced mouse model and human skin cells. Our findings revealed enhanced cutaneous penetration of gold nanorod and dexamethasone conjugates compared with that of dexamethasone, owing to superior skin penetration. Gold nanorod and dexamethasone conjugates demonstrated an optimal pharmacological impact at minimal dosages without toxicity during extended use. To further enhance the effectiveness of gold nanorod and dexamethasone conjugates, 808 nm near-infrared laser irradiation, which reacts to gold, was additionally applied to achieve thermal elevation to expedite drug skin penetration. Supplementary laser irradiation at 808 nm significantly ameliorated psoriatic symptoms following deep gold nanorod and dexamethasone conjugates penetration. This corresponded with restored peroxisome proliferator-activated receptor-γ levels and accelerated dexamethasone release from the gold nanorod and dexamethasone conjugates complex. These findings highlight the potential of gold nanorod and dexamethasone conjugates to enhance drug penetration through dermal layers, thereby aiding psoriasis treatment. Moreover, its compatibility with photothermal therapy offers prospects for novel therapeutic interventions across various inflammatory skin disorders.

Nanographene-Au fine-tuning to intensify plasmonic-resonance of polymeric hybrid bionanosystem for synergistic phototherapy and nerve photobiomodulation.

Here, we report the multi-photo-bioactivity of the plasmonic-nano graphitic coordinated polycaprolactone-based aligned nanofibrous scaffolds-based bionanosystem for photothermal breast and colon cancer therapies and peripheral nerve photobiomodulation. The size-optimized colloidal reduced graphene oxide (nRGO, 180 nm) nanosheets, for enhanced photothermal impact, were surface-functionalized with gold nanospheres (AuNPs) to prepare the nRGO@AuNP monodispersed nano-composite and then doped 2.0 mg of nRGO@AuNP in biocompatible and biodegradable polymer polycaprolactone (PCL) to fabricate the nRGO@AuNP-PCL (2.0 mg) plasmonic aligned nanofibrous scaffolds. More than 90% of cancer cells, breast cancer (MCF-7) as well as colon cancer (CT-26), ablated after 5 min of low NIR (808 nm) laser power (0.72 W/cm2) illumination with nRGO@AuNP-PCL (2.0 mg) aligned nanofibrous scaffolds. Besides, the nRGO@AuNP-PCL (2.0 mg) provided an extraordinary microenvironment for adhesion, nerve growth, proliferation, and differentiation of PC12 and S42 cells which mimics the natural extracellular matrix. The 2.5-fold increase in neurite length was observed with NIR illumination after 3 days whereas 1.7-fold was found without NIR illumination after 7 days in comparison to PCL (pure). The current findings will be useful to provide a new crucial approach for preparing biocompatible multifunctional composite plasmonic nanofibers as a highly efficient distinct platform for photothermal therapies and promising bioimplants to overcome the loss of sensation after cancer surgery through nerve photobiomodulation.

"Four-in-One" Nanozyme for Amplified Catalytic-Photothermal Therapy.

The cancer therapeutic efficacy of the peroxidase (POD)-mimicking nanozyme-based monotherapy is significantly hindered due to insufficient intratumoral hydrogen peroxide (H2O2) and glutathione (GSH) consumption effect on reactive oxygen species (ROS). In this study, we present the development of poly(o-phenylenediamine)@gold nanoparticles (AuNPs) (PoPD@Au) nanocomposites for multifunctional catalytic-photothermal therapy. These nanocomposites exhibit triple distinct nanozymatic activities, i.e., POD-like activity that catalyzes H2O2 to ROS, glucose oxidase (GOx)-like activity that supplements endogenous H2O2, and GSH depleting activity that decreases the ROS consumption efficiency. This open source and reduce expenditure strategy for ROS generation allows for the amplification of tumor oxidative stress, thereby enhancing anti-tumor efficiency. Additionally, the PoPD@Au nanocomposites demonstrate outstanding photothermal conversion efficiency, contributing to the synergistic effect between PoPD and AuNPs. Moreover, we reveal the improved photothermal performance of PoPD@Au triggered by the tumor microenvironment pH, which provides additional benefits for targeted catalytic-photothermal therapy. This "four-in-one" design of PoPD@Au enables efficient anti-tumor effects both in vitro and in vivo, making it a universal strategy for engineering catalytic-photothermal therapeutic nanoagents.

Clonogenic assay and computational modeling using real cell images to study physical enhancement and cellular sensitization induced by metal nanoparticles under MV and kV X-ray irradiation.

This study was initiated due to the physically unexplainable tumor controls resulting from metal nanoparticle (MNP) experiments even under MV X-ray irradiation. A more accurate explanation of the mechanism of radiosensitization induced by MNP is warranted, considering both its physical dose enhancement and biological sensitization, as related research is lacking. Thus, we aimed to examine the intricate dynamics involved in MNP-induced radiosensitization. We conducted specifically designed clonogenic assays for the A549 lung cancer cell line with MNP irradiated by 6 MV and 300 kVp X-rays. Two types of MNP were employed: one based on iron oxide, promoting ferroptosis, and the other on gold nanoparticles known for inducing a significant dose enhancement, particularly at low-energy X-rays. We introduced the lethality enhancement factor (LEF) as the fraction in the cell killing attributed to biological sensitization. Subsequently, Monte Carlo simulations were conducted to evaluate the radial dose profiles for each MNP, corresponding to the physical enhancement. Finally, the local effect model was applied to the clonogenic assay results on real cell images. The LEF and the dose enhancement in the cytoplasm were incorporated to increase the accuracy in the average lethal events and, consequently, in the survival fraction. The results reveal an increased cell killing for both of the MNP under MV and kV X-ray irradiation. In both types of MNP, the LEF reveals a biological sensitization evident. The sensitizer enhancement ratio, derived from the calculations, exhibited only 3% and 1% relative differences compared to the conventional linear-quadratic model for gold and ferroptosis inducer nanoparticles, respectively. These findings indicate that MNPs sensitize cells via radiation through mechanisms akin to ferroptosis inducers, not exclusively relying on a physical dose enhancement. Their own contributions to survival fractions were successfully integrated into computational modeling.

Modulation of calcium-influx by carboxymethyl tamarind­gold nanoparticles promotes biomineralization for tissue regeneration.

Gold nanoparticles (AuNPs) have been reported to modulate bone tissue regeneration and are being extensively utilized in biomedical implementations attributable to their low cytotoxicity, biocompatibility and simplicity of functionalization. Lately, biologically synthesized nanoparticles have acquired popularity because of their environmentally acceptable alternatives for diverse applications. Here we report the green synthesis of AuNPs by taking the biopolymer Carboxymethyl Tamarind (CMT) as a unique reducing as well as a stabilizing agent. The synthesized CMT-AuNPs were analyzed by UV-vis spectrophotometer, DLS, FTIR, XRD, TGA, SEM and TEM. These results suggest that CMT-AuNPs possess an average size of 19.93 ± 8.52 nm and have long-term stability. Further, these CMT-AuNPs promote the proliferation together with the differentiation and mineralization of osteoblast cells in a "dose-dependent" manner. Additionally, CMT-AuNPs are non-toxic to SD rats when applied externally. We suggest that the CMT-AuNPs have the potential to be a suitable and non-toxic agent for differentiation and mineralization of osteoblast cells in vitro and this can be tested in vivo as well.

NIR-Active Gold Dogbone Nanorattles Impregnated in Cationic Dextrin Nanoparticles for Cancer Nanotheranostics.

Theranostic systems, which integrate therapy and diagnosis into a single platform, have gained significant attention as a promising approach for noninvasive cancer treatment. The field of image-guided therapy has revolutionized real-time tumor detection, and within this domain, plasmonic nanostructures have garnered significant attention. These structures possess unique localized surface plasmon resonance (LSPR), allowing for enhanced absorption in the near-infrared (NIR) range. By leveraging the heat generated from plasmonic nanoparticles upon NIR irradiation, target cancer cells can be effectively eradicated. This study introduces a plasmonic gold dogbone-nanorattle (AuDB NRT) structure that exhibits broad absorption in the NIR region and demonstrates a photothermal conversion efficiency of 35.29%. When exposed to an NIR laser, the AuDB NRTs generate heat, achieving a maximum temperature rise of 38 °C at a concentration of 200 µg/mL and a laser power density of 3 W/cm2. Additionally, the AuDB NRTs possess intrinsic electromagnetic hotspots that amplify the signal of a Raman reporter molecule, making them an excellent probe for surface-enhanced Raman scattering-based bioimaging of cancer cells. To improve the biocompatibility of the nanorattles, the AuDB NRTs were conjugated with mPEG-thiol and successfully encapsulated into cationic dextrin nanoparticles (CD NPs). Biocompatibility tests were performed on HEK 293 A and MCF-7 cell lines, revealing high cell viability when exposed to AuDB NRT-CD NPs. Remarkably, even at a low laser power density of 1 W/cm2, the application of the NIR laser resulted in a remarkable 80% cell death in cells treated with a nanocomposite concentration of 100 µg/mL. Further investigation elucidated that the cell death induced by photothermal heat followed an apoptotic mechanism. Overall, our findings highlight the significant potential of the prepared nanocomposite for cancer theranostics, combining effective photothermal therapy along with the ability to image cancer cells.

Bionic nanotheranostic for multimodal imaging-guided NIR-II-photothermal cancer therapy.

In photothermal therapy (PTT), the photothermal conversion of the second near-infrared (NIR-II) window allows deeper penetration and higher laser irradiance and is considered a promising therapeutic strategy for deep tissues. Since cancer remains a leading cause of deaths worldwide, despite the numerous treatment options, we aimed to develop an improved bionic nanotheranostic for combined imaging and photothermal cancer therapy. We combined a gold nanobipyramid (Au NBP) as a photothermal agent and MnO2 as a magnetic resonance enhancer to produce core/shell structures (Au@MnO2; AM) and modified their surfaces with homologous cancer cell plasma membranes (PM) to enable tumour targeting. The performance of the resulting Au@MnO2@PM (AMP) nanotheranostic was evaluated in vitro and in vivo. AMP exhibits photothermal properties under NIR-II laser irradiation and has multimodal in vitro imaging functions. AMP enables the computed tomography (CT), photothermal imaging (PTI), and magnetic resonance imaging (MRI) of tumours. In particular, AMP exhibited a remarkable PTT effect on cancer cells in vitro and inhibited tumour cell growth under 1064 nm laser irradiation in vivo, with no significant systemic toxicity. This study achieved tumour therapy guided by multimodal imaging, thereby demonstrating a novel strategy for the use of bionic gold nanoparticles for tumour PTT under NIR-II laser irradiation.

Multifunctional Metal-Phenolic Composites Promote Efficient Periodontitis Treatment via Antibacterial and Osteogenic Properties.

Periodontitis, a complex inflammatory disease initiated by bacterial infections, presents a significant challenge in public health. The increased levels of reactive oxygen species and the subsequent exaggerated immune response associated with periodontitis often lead to alveolar bone resorption and tooth loss. Herein, we develop multifunctional metal-phenolic composites (i.e., Au@MPN-BMP2) to address the complex nature of periodontitis, where gold nanoparticles (AuNPs) are coated by metal-phenolic networks (MPNs) and bone morphogenetic protein 2 (BMP2). In this design, MPNs exhibit remarkable antibacterial and antioxidant properties, and AuNPs and BMP2 promote osteogenic differentiation of bone marrow mesenchymal stem cells under inflammatory conditions. In a rat model of periodontitis, treatment with Au@MPN-BMP2 leads to notable therapeutic outcomes, including mitigated oxidative stress, reduced progression of inflammation, and the significant prevention of inflammatory bone loss. These results highlight the multifunctionality of Au@MPN-BMP2 nanoparticles as a promising therapeutic approach for periodontitis, addressing both microbial causative factors and an overactivated immune response. We envision that the rational design of metal-phenolic composites will provide versatile nanoplatforms for tissue regeneration and potential clinical applications.