Liposomal formulation of a gold(III) metalloantibiotic: a promising strategy against antimicrobial resistance.

A novel lipoformulation was developed by encapsulating cationic (S^C)-cyclometallated gold(III) complex [Au(dppta)(N2Py-PZ-dtc)]+ (AuPyPZ) in liposomes. The liposomal form of compound AuPyPZ has a bactericidal action similar to that of the free drug without any appreciable effect on the viability of mammalian cells. Furthermore, the nanoformulation reduces metalloantibiotic-induced inhibition of hERG and the inhibition of cytochromes, significantly decreasing the potential liabilities of the metallodrug. The obtained metalloantibiotic liposomal formulation shows high stability and suitable properties for drug delivery, representing an effective strategy to fight against drug-resistant bacteria.

6-gingerol effect on rat liver following exposure to gold nanoparticles: From histopathologic findings to inflammatory and oxidative stress biomarkers.

Gold nanoparticles (AuNPs) have unique features which could be beneficial to various aspects of clinics and industry. Long-term exposure to AuNPs damages the physiologic functions and tissue structure of organs. Gingerol has anti-inflammatory and antioxidant properties. This study explored the effect of 6-gingerol on alleviation of AuNPs exposure effects in rats' liver. Thirty-two male Wistar rats were randomly assigned to four groups of negative control (received no AuNPs or treatment), positive control (received AuNPs but not treatment), and two study arms (both received AuNPs and one group 50 and the other 100 mg/Kg body weight 6-gingerol). All injections were performed intraperitoneally. After 30 days, serum levels of ALP, AST, ALT were assessed through ELISA method by an autoanalyzer while GGT, SOD, GPx, CAT, IL-6, IL-1ß, TNF-α, CRP, 8-OHdG, MDA, and Bax/Bcl2 were measured using an ELISA reader. Paraffin-embedded tissue sections of the livers from all groups were also prepared and H&E staining was performed on them for investigation of tissue changes. Statistical analyses were performed using SPSS version 26 and p = 0.05 was considered as the level of significancy. AuNPs exposure significantly increased the levels of ALP, AST, ALT, GGT, CRP, IL-6, IL-1ß, TNF-α, Bax/Bcl2, 8-OHdG, MDA (p < 0.001) in positive control groups compared to negative controls, while treatment with 6-gingerol significantly decreased the mentioned enzyme levels (p < 0.001). The level of antioxidant enzymes of SOD, GPx, and CAT, on the other hand, was found to be highest and lowest in negative and positive controls, respectively (p < 0.001). Treatment with 6-gingerol significantly decreased the mentioned enzyme levels (p < 0.001). Histology results showed no signs of degeneration, necrosis, or immune cell infiltration in negative controls, while positive controls showed dilated central veins and hyperemia along with infiltration of mononuclear immune cells to the portal area, tissue degeneration, and necrosis. The study arms showed improved signs as they showed normal trabecular structures with no clear portal space. Treatment with 6-gingerol seems to significantly and efficiently reduce the hepatic side effects of AuNPs exposure in Wistar rats.

Synthesis, Chemical Characterization, and Biological Evaluation of Hydrophilic Gold(I) and Silver(I) N-Heterocyclic Carbenes as Potential Anticancer Agents.

A series of new gold(I) and silver(I) N-heterocyclic carbenes bearing a 1-thio-ß-d-glucose tetraacetate moiety was synthesized and chemically characterized. The compounds' stability and solubility in physiological conditions were investigated employing a multitechnique approach. Interaction studies with biologically relevant proteins, such as superoxide dismutase (SOD) and human serum albumin (HSA), were conducted via UV-vis absorption spectroscopy and high-resolution ESI mass spectrometry. The biological activity of the compounds was evaluated in the A2780 and A2780R (cisplatin-resistant) ovarian cancer cell lines and the HSkMC (human skeletal muscle) healthy cell line. Inhibition studies of the selenoenzyme thioredoxin reductase (TrxR) were also carried out. The results highlighted that the gold complexes are more stable in aqueous environment and capable of interaction with SOD and HSA. Moreover, these carbenes strongly inhibited the TrxR activity. In contrast, the silver ones underwent structural alterations in the aqueous medium and showed greater antiproliferative activity.

Chemo-photothermal therapy of bacterial infections using metal-organic framework-integrated polymeric network coatings.

Surface modification of biomedical materials and devices using versatile nanocomposite coatings holds great promise for improving functionalities to defend against life-threatening bacterial infections. In this study, a one-step surface modification strategy was developed to deposit gold nanorods (AuNRs)- and curcumin (CUR)-encapsulated zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (AuNRs-ZIF-CUR NPs or AZC) onto phytic acid (PA)-ε-polylysine (Ply) network coatings. In the solution mixture of PA, Ply and AZC, PA interacted with Ply via electrostatic interactions, and can also bind to AZC via metal chelation. The as-formed AZC-PA-Ply aggregates could be deposited onto various substrates via surface adhesion of PA and gravitational effects. The physicochemical and antibacterial properties of the AZC-PA-Ply network coatings on polydimethylsiloxane (PDMS) substrates were evaluated. The sustained release of zinc ions and CUR, as well as the contact-killing ability of Ply, endowed the AZC-PA-Ply network coatings with good antibacterial chemotherapeutic effects. In addition, the embedded AuNRs in the AZC-PA-Ply network coatings exhibited excellent photothermal conversion efficiency for the ablation of bacteria. Upon near-infrared (NIR) laser irradiation, the AZC-PA-Ply-coated PDMS surfaces exhibited strong antibacterial effects by disrupting the membrane integrity and cellular functions of the adhered bacteria. Thus, the AZC-PA-Ply network coatings displayed combined antibacterial chemotherapeutic and photothermal therapeutic effects. Furthermore, the AZC-PA-Ply-coated PDMS substrates exhibited effective bacterial infection prevention and good biocompatibility in an in vivo implant model. Hence, the versatile AZC-PA-Ply network coatings are potentially useful as a multi-modal antibacterial platform to eliminate infectious bacterial pathogens in biomedical applications.

Metal(triphenylphosphine)-atovaquone Complexes: Synthesis, Antimalarial Activity, and Suppression of Heme Detoxification.

To ascertain the bioinorganic chemistry of metals conjugated with quinones, the complexes [Ag(ATV)(PPh3)2] (1), [Au(ATV)(PPh3)]·2H2O (2), and [Cu(ATV)(PPh3)2] (3) were synthesized by the coordination of the antimalarial naphthoquinone atovaquone (ATV) to the starting materials [Ag(PPh3)2]NO3, [Au(PPh3)Cl], and [Cu(PPh3)2NO3], respectively. These complexes were characterized by analytical and spectroscopical techniques. X-ray diffraction of single crystals precisely confirmed the coordination mode of ATV to the metals, which was monodentate or bidentate, depending on the metal center. Both coordination modes showed high stability in the solid state and in solution. All three complexes showed negative log D values at pH 5, but at pH 7.4, while complex 2 continued to have a negative log D value, complexes 1 and 3 displayed positive values, indicating a more hydrophilic character. ATV and complexes 1-3 could bind to ferriprotoporphyrin IX (FePPIX); however, only complexes 1-3 could inhibit ß-hematin crystal formation. Phenotype-based activity revealed that all three metal complexes are able to inhibit the growth of P. falciparum with potency and selectivity comparable to those of ATV, while the starting materials lack this activity. The outcomes of this chemical design may provide significant insights into structure-activity relationships for the development of new antimalarial agents.

Photo-triggered AuAg@g-C3N4 composite nanoplatform for multimodal broad-spectrum antibacterial therapy.

Strategies based on nanomaterials for sterilization address the problem of antibiotic resistance faced by conventional antimicrobials, with the contribution of photocatalytic compounds being particularly prominent. Herein, to integrate multiple bactericidal techniques into a system for generating synergistic antibacterial effects, a novel photo-triggered AuAg@g-C3N4 composite nanoplatform was constructed by anchoring AuAg on the surface of a g-C3N4 layer. As the composite nanoplatform had a lower bandgap and superior visible light utilization efficiency, it could facilitate free electron transfer better and exhibit superior photocatalytic activity under light conditions. Moreover, the AuAg@g-C3N4 composite nanoplatform integrated the bactericidal modes of silver ion toxicity, physical disruption of bacterial cell membranes by the multilayer structure, and excellent photocatalytic activity, exhibiting extremely superior bactericidal effects against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis, with a bactericidal efficiency of up to 100%.

Nucleic acid-functionalized gold nanoparticles as intelligent photothermal therapy agents for precise cancer treatment.

We present an intelligent photothermal therapy agents by functionalizing gold nanoparticles with specific nucleic acid sequences. Hairpin nucleic acids are modified to the nanoparticles, forming AuNPs-1 and AuNPs-2. Upon infiltrating cancer cells, these nanoparticles undergo catalytic hairpin assembly in the presence of target miRNA, leading to aggregation and subsequent photothermal conversion. Under near-infrared laser irradiation, aggregated gold nanoparticles exhibit efficient photothermal conversion, selectively damaging cancer cells. This approach offers heightened selectivity, as nanoparticles only aggregate in environments with cancer biomarkers present, sparing normal cells. Cytotoxicity assays confirm minimal toxicity to normal cells. In vivo studies on mice bearing solid tumors validate the system's efficacy in tumor regression. Overall, this study highlights the potential of nucleic acid-functionalized gold nanoparticles in intelligent and selective cancer photothermal therapy, offering insights for targeted diagnosis and treatment development.

Antibacterial activity of Au(I), Pt(II), and Ir(III) biotin conjugates prepared by the iClick reaction: influence of the metal coordination sphere on the biological activity.

A series of biotin-functionalized transition metal complexes was prepared by iClick reaction from the corresponding azido complexes with a novel alkyne-functionalized biotin derivative ([Au(triazolatoR,R')(PPh3)], [Pt(dpb)(triazolatoR,R')], [Pt(triazolatoR,R')(terpy)]PF6, and [Ir(ppy)(triazolatoR,R')(terpy)]PF6 with dpb = 1,3-di(2-pyridyl)benzene, ppy = 2-phenylpyridine, and terpy = 2,2':6',2''-terpyridine and R = C6H5, R' = biotin). The complexes were compared to reference compounds lacking the biotin moiety. The binding affinity toward avidin and streptavidin was evaluated with the HABA assay as well as isothermal titration calorimetry (ITC). All compounds exhibit the same binding stoichiometry of complex-to-avidin of 4:1, but the ITC results show that the octahedral Ir(III) compound exhibits a higher binding affinity than the square-planar Pt(II) complex. The antibacterial activity of the compounds was evaluated on a series of Gram-negative and Gram-positive bacterial strains. In particular, the neutral Au(I) and Pt(II) complexes showed significant antibacterial activity against Staphylococcus aureus and Enterococcus faecium at very low micromolar concentrations. The cytotoxicity against a range of eukaryotic cell lines was studied and revealed that the octahedral Ir(III) complex was non-toxic, while the square-planar Pt(II) and linear Au(I) complexes displayed non-selective micromolar activity.

Development of Amphotericin B Decorated Gold Nanoparticles as a Promising Antileishmanial Nanoconjugate.

Leishmaniasis, attributed to the protozoan parasite Leishmania, manifests in diverse clinical forms, including cutaneous, mucocutaneous, and visceral leishmaniasis; VL constitutes a significant global health menace. Prevalent in tropical and subtropical regions, this affliction disproportionately impacts individuals below the poverty threshold, transmitted through the bite of female sandflies. Existing treatments, such as pentavalent antimony, miltefosine, and Amphotericin B, exhibit limitations. Despite the emergence of liposomal Amphotericin B (AmBisome) as a promising antileishmanial agent, its utility is impeded by adverse effects, elevated production expenses, and cytotoxicity. To address these challenges, our investigation introduces a potential remedy─a citrate-coated gold Amphotericin B nanoparticle formulation. Characterized using dynamic light scattering and transmission electron microscopy, this pioneering formulation exhibited efficacy against L. donovani Ag83 promastigotes as demonstrated by MTT cell viability testing. Evaluating internal reactive oxygen species (ROS) levels and dual staining with acridine orange and ethidium bromide unveiled its consequential impact on cell death. Significantly, our study discloses this novel nanoformulation's unprecedented inhibition of the trypanothione reductase enzyme. The findings posit the citrate-coated gold Amphotericin B nanoformulation as a promising and targeted antileishmanial agent, representing potential advancements in leishmaniasis therapeutics.

A New Class of Gold(I) NHC Complexes with Proapoptotic and Resensitizing Properties towards Multidrug Resistant Leukemia Cells Overexpressing BCL-2.

From previous studies, it is evident that metal-organic gold(I) complexes have antiproliferative activities. The aim of this study is not only to find new anticancer agents but also to overcome existing cytostatic resistance in cancer cells. The synthesis and medicinal evaluation of two cationic 1,3-disubstituted gold(I) bis-tetrazolylidene complexes 1 and 2 are reported. To determine apoptosis-inducing properties of the complexes, DNA fragmentation was measured using propidium iodide staining followed by flow cytometry. Gold(I) complex 1 targets explicitly malignant cells, effectively inhibiting their growth and selectively inducing apoptosis without signs of necrosis. Even in cells resistant to common treatments such as doxorubicin, it overcomes multidrug resistance and sensitizes existing drug-resistant cells to common cytostatic drugs. It is assumed that gold(I) complex 1 involves the mitochondrial pathway in apoptosis and targets members of the BCL-2 family, enhancing its potential as a therapeutic agent in cancer treatment.

Immobilizing DNase in ternary AuAgCu hydrogels to accelerate biofilm disruption for synergistically enhanced therapy of MRSA infections.

Bacterial biofilm-related infections have become a significant global concern in public health and economy. Extracellular DNA (eDNA) is regarded as one of the key elements of extracellular polymeric substances (EPS) in bacterial biofilm, providing robust support to maintain the stability of bacterial biofilms for fighting against environmental stresses (such as antibiotics, reactive oxygen species (ROS), and hyperthermia). In this study, ternary AuAgCu hydrogels nanozyme with porous network structures were utilized for the immobilization of DNase (AuAgCu@DNase hydrogels) to realize enhanced biofilm decomposition and antibacterial therapy of MRSA. The prepared AuAgCu@DNase hydrogels can efficiently hydrolyze eDNA in biofilms so that the generated ROS and hyperthermia by laser irradiation can permeate into the interior of the biofilm to achieve deep sterilization. The typical interface interactions between AuAgCu hydrogels and DNase and the excellent photothermal-boost peroxidase-like performances of AuAgCu hydrogels take responsibility for the enhanced antibacterial activity. In the MRSA-infected wounds model, the in vivo antibacterial results revealed that the AuAgCu@DNase hydrogels possess excellent drug-resistant bacteria-killing performance with superb biocompatibility. Meanwhile, the pathological analysis of collagen deposition and fibroblast proliferation of wounds demonstrate highly satisfactory wound healing. This work offers an innovative path for developing nanozyme-enzyme antibacterial composites against drug-resistant bacteria and their biofilms.

Photothermal induction of pyroptosis in malignant glioma spheroids using (16-mercaptohexadecyl)trimethylammonium bromide-modified cationic gold nanorods.

Plasmonic photothermal therapy (PPTT) employing plasmonic gold nanorods (GNRs) presents a potent strategy for eradication of tumors including aggressive brain gliomas. Despite its promise, there is a pressing need for a more comprehensive evaluation of PPTT using sophisticated in vitro models that closely resemble tumor tissues, thereby facilitating the elucidation of therapeutic mechanisms. In this study, we exposed 3D glioma spheroids (tumoroids) to (16-mercaptohexadecyl)trimethylammonium bromide-functionalized gold nanorods (MTAB-GNRs) and a near-infrared (NIR) laser. We demonstrate that the photothermal effect can be fine-tuned by adjusting the nanoparticle concentration and laser power. Depending on the selected parameters, the laser can trigger either regulated or non-regulated cell death (necrosis) in both mouse GL261 and human U-87 MG glioma cell lines, accompanied by translocation of phosphatidylserine in the membrane. Our investigation into the mechanism of regulated cell death induced by PPTT revealed an absence of markers associated with classical apoptosis pathways, such as cleaved caspase 3. Instead, we observed the presence of cleaved caspase 1, gasdermin D, and elevated levels of NLRP3 in NIR-irradiated tumoroids, indicating the activation of pyroptosis. This finding correlates with previous observations of lysosomal accumulation of MTAB-GNRs and the known lysosomal pathway of pyroptosis activation. We further confirmed the absence of toxic breakdown products of GNRs using electron microscopy, which showed no melting or fragmentation of gold nanoparticles under the conditions causing regulated cell death. In conclusion, PPTT using coated gold nanorods offers significant potential for glioma cell elimination occurring through the activation of pyroptosis rather than classical apoptosis pathways.

Comparative Study of Antioxidant Activity of Dextran-Coated Iron Oxide, Gold, and Silver Nanoparticles Against Age-Induced Oxidative Stress in Erythrocytes.

Erythrocytes undergo several changes during human aging and age-related diseases and, thus, have been studied as biomarkers of the aging process. The present study aimed to explore the antioxidant ability of metal and metal oxide nanoparticles (NPs) such as iron oxide (Fe3O4), gold (Au), and silver (Ag) to mitigate age-related oxidative stress in human erythrocytes. Metal and metal oxide NPs behave like antioxidative enzymes, directly influencing redox pathways and thus have better efficiency. Additionally, biopolymer coatings such as dextran enhance the biocompatibility of these NPs. Therefore, dextran-coated Fe3O4, Au, and Ag NPs were synthesized using wet chemical methods and were characterized. Their hemocompatibility and ability to protect erythrocytes from age-induced oxidative stress were investigated. The Fe3O4 and Au NPs were observed to protect erythrocytes from hydrogen peroxide and age-induced oxidative damage, including decreased antioxidant levels, reduced activity of antioxidative enzymes, and increased amounts of oxidative species. Pretreatment with NPs preserved the morphology and membrane integrity of the erythrocyte. However, Ag NPs induced oxidative stress in erythrocytes similar to hydrogen peroxide. Therefore, dextran-coated Fe3O4 and Au nanoparticles have the potential to be employed as antioxidant therapies against age-related oxidative stress.

Hypoxia Reversion and STING Pathway Activation through Large Mesoporous Nanozyme for Near-Infrared-II Light Amplified Tumor Polymetallic-Immunotherapy.

cGAS/STING pathway, which is highly related to tumor hypoxia, is considered as a potential target for remodeling the immunosuppressive microenvironment of solid tumors. Metal ions, such as Mn2+, activate the cGAS/STING pathway, but their efficacy in cancer therapy is limited by insufficient effect on immunogenic tumor cell death of a single ion. Here, we evaluate the association between tumor hypoxia and cGAS/STING inhibition and report a polymetallic-immunotherapy strategy based on large mesoporous trimetal-based nanozyme (AuPdRh) coordinated with Mn2+ (Mn2+@AuPdRh) to activate cGAS/STING signaling for robust adaptive antitumor immunity. Specifically, the inherent CAT-like activity of this polymetallic Mn2+@AuPdRh nanozyme decomposes the endogenous H2O2 into O2 to relieve tumor hypoxia induced suppression of cGAS/STING signaling. Moreover, the Mn2+@AuPdRh nanozyme displays a potent near-infrared-II photothermal effect and strong POD-mimic activity; and the generated hyperthermia and •OH radicals synergistically trigger immunogenic cell death in tumors, releasing abundant dsDNA, while the delivered Mn2+ augments the sensitivity of cGAS to dsDNA and activates the cGAS-STING pathway, thereby triggering downstream immunostimulatory signals to kill primary and distant metastatic tumors. Our study demonstrates the potential of metal-based nanozyme for STING-mediated tumor polymetallic-immunotherapy and may inspire the development of more effective strategies for cancer immunotherapy.

Novel gold-based complex GC7 suppresses cancer cell proliferation via impacting energy metabolism mediated by mitochondria.

Due to their pivotal roles in regulating energy metabolism and apoptosis, mitochondria in cancer cells have been considered a vulnerable and feasible target. Many anticancer agents, e.g., metal-based compounds, are found to target and disturb mitochondria primarily, which may lead to the disturbance of energy metabolism and, more importantly, the initiation of apoptosis. In this work, a gold-based complex 7 (GC7) was synthesized and evaluated in a series of different cancer cell lines. The anticancer efficacies of GC7 on cell viability, apoptosis, and colony formation were determined. Cellular thioredoxin reductase (TrxR) activity, oxygen consumption rate (OCR), glucose uptake, and lactate production following GC7 treatment were evaluated and analyzed. The Jeko-1 and A549 xenograft models were used to assess GC7's tumor-suppressing effects. The results showed that GC7 possessed a broad-spectrum anticancer effect, with IC50 values ranging from 0.43 to 1.2 µM in multiple cancer cell lines, which was more potent than gold-based auranofin (∼2-6 folds). GC7 (0.3 and 1 µM) efficiently induced apoptosis of Jeko-1, A549, and HCT116 cells, and it suppressed the sphere formation of cancer stem cells GSC11 and GSC23 cells at 0.1 µM, and it completely eliminated colony at 0.3 µM. The preliminary mechanistic study showed that GC7 inhibited cellular TrxR activity, suppressed mitochondrial OCR, reduced mitochondrial membrane potential (MMP), decreased glucose uptake, and possibly suppressed glycolysis to reduce lactate production. GC7 was predicted to have a similar yet slightly different pharmacokinetic profile as auranofin. Finally, GC7 (20 mg/kg, oral, 5/week, or 3 mg/kg, IP, 3/week) significantly inhibited tumor growth. In conclusion, GC7 showed great potential in suppressing cancer cell proliferation, probably via inhibiting TrxR and impacting mitochondria-mediated energy metabolism.

Design, synthesis and biological evaluation of multitarget hybrid molecules containing NHC-Au(I) complexes and carbazole moieties.

N-heterocyclic carbenes (NHCs) represent suitable ligands for rapid and efficient drug design, because they offer the advantage of being easily chemically modified and can bind several substituents, including transition metals as, for instance, gold derivatives. Gold-NHC complexes possess various biological activities and were demonstrated good candidates as anticancer drugs. Besides, carbazole derivatives are characterized by various pharmacological properties, such as anticancer, antibacterial, anti-inflammatory, and anti-psychotropic. Amongst the latter, N-thioalkyl carbazoles were proved to inhibit cancer cells damaging the nuclear DNA, through the inhibition of human topoisomerases. Herein, we report the design, synthesis and biological evaluation of nine new hybrid molecules in which NHC-Au(I) complexes and N-alkylthiolated carbazoles are linked together, in order to obtain novel biological multitarget agents. We demonstrated that the lead hybrid complexes possess anticancer, anti-inflammatory and antioxidant properties, with a high potential as useful tools for treating distinct aspects of several diseases, amongst them cancer.

iRGD-Guided Silica/Gold Nanoparticles for Efficient Tumor-Targeting and Enhancing Antitumor Efficacy Against Breast Cancer.

Background: Breast cancer presents significant challenges due to the limited effectiveness of available treatments and the high likelihood of recurrence. iRGD possesses both RGD sequence and C-terminal sequence and has dual functions of targeting and membrane penetration. iRGD-modified nanocarriers can enhance drug targeting of tumor vascular endothelial cells and penetration of new microvessels, increasing drug concentration in tumor tissues. Methods: The amidation reaction was carried out between SiO2/AuNCs and iRGD/PTX, yielding a conjugated drug delivery system (SiO2/AuNCs-iRGD/PTX, SAIP@NPs). The assessment encompassed the characterization of the morphology, particle size distribution, physicochemical properties, in vitro release profile, cytotoxicity, and cellular uptake of SAIP@NPs. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed using a small animal in vivo imaging system and a tumor-bearing nude mice model, respectively. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed utilizing a small animal in vivo imaging system and an in situ nude mice breast cancer xenograft model, respectively. Results: The prepared SAIP@NPs exhibited decent stability and a certain slow-release effect in phosphate buffer (PBS, pH 7.4). In vitro studies had shown that, due to the dual functions of transmembrane and targeting of iRGD peptide, SAIP@NPs exhibited strong binding to integrin αvß3, which was highly expressed on the membrane of MDA-MB-231 cells, improving the uptake capacity of tumor cells, inhibiting the rapid growth of tumor cells, and promoting tumor cell apoptosis. The results of animal experiments further proved that SAIP@NPs had longer residence time in tumor sites, stronger anti-tumor effect, and no obvious toxicity to major organs of experimental animals. Conclusion: The engineered SAIP@NPs exhibited superior functionalities including efficient membrane permeability, precise tumor targeting, and imaging, thereby significantly augmenting the therapeutic efficacy against breast cancer with a favorable safety profile.

Near infrared-II photothermal-promoted multi-enzyme activities of gold-platinum to enhance catalytic therapy.

Bimetallic nanozymes exhibited multi-enzyme activities, but glutathione (GSH) overexpression and weak catalytic capability restricted their catalytic therapeutic performance. Thus, this study developed a smart nanozyme (AuPt@MnO2) with a core-shell structure by coating manganese dioxide (MnO2) on the gold-platinum (AuPt) nanozyme (AuPt@MnO2) surface to enhance catalytic therapy. In this nanozyme, AuPt possessed triple-enzyme activities, i.e., catalase, peroxidase, and glucose oxidase, which greatly improved oxygen, hydroxyl radicals (·OH), and hydrogen peroxide generation, due to cyclic reactions. Moreover, GSH consumption degraded the MnO2 shell, which then enhanced ·OH generation of Mn2+. More importantly, the near-infrared-II (NIR-II) photothermal performance of AuPt@MnO2 with a high conversion efficiency of 38.7 % further promoted multi-enzyme activities and enhanced catalytic therapy. Moreover, combining NIR-II photothermal therapy and enhancing catalytic therapy decreased the cell viability to 10.8 %, and thereby, the tumors were cleared. Thus, the AuPt@MnO2 smart nanoplatform developed in this study exhibited NIR-II photothermal-promoted multi-enzyme activities and excellent antitumor efficacy, which will be promising for enhancing catalytic therapy.

Antibacterial Mechanism of d-Cysteine/Polyethylene Glycol-Functionalized Gold Nanoparticles and Their Potential for the Treatment of Bacterial Infections.

Bacterial infection has always posed a severe threat to public health. Gold nanoparticles (Au NPs) exhibit exceptional biocompatibility and hold immense potential in biomedical applications. However, their antibacterial effectiveness is currently unsatisfactory. Herein, a chiral antibacterial agent with high stability was prepared by the modification of Au NPs with d-cysteine with the assistance of polyethylene glycol (PEG). The as-synthesized d-cysteine/PEG-Au NPs (D/P-Au NPs) exhibited a stronger (99.5-99.9%) and more stable (at least 14 days) antibacterial performance against Gram-negative (Escherichia coli and Listeria monocytogenes) and Gram-positive (Salmonella enteritidis and Staphylococcus aureus) bacteria, compared with other groups. The analysis of the antibacterial mechanism revealed that the D/P-Au NPs mainly affected the assembly of ribosomes, the biosynthesis of amino acids and proteins, as well as the DNA replication and mismatch repair, ultimately leading to bacterial death, which is significantly different from the mechanism of reactive oxygen species-activated metallic antibacterial NPs. In particular, the D/P-Au NPs were shown to effectively accelerate the healing of S. aureus-infected wounds in mice to a rate comparable to or slightly higher than that of vancomycin. This work provides a novel approach to effectively design chiral antibacterial agents for bacterial infection treatment.

Silver/gold nanoalloy implant coatings with antibiofilm activity via pH-triggered silver ion release.

Implant infections are a major challenge for the healthcare system. Biofilm formation and increasing antibiotic resistance of common bacteria cause implant infections, leading to an urgent need for alternative antibacterial agents. In this study, the antibiofilm behaviour of a coating consisting of a silver (Ag)/gold (Au) nanoalloy is investigated. This alloy is crucial to reduce uncontrolled potentially toxic Ag+ ion release. In neutral pH environments this release is minimal, but the Ag+ ion release increases in acidic microenvironments caused by bacterial biofilms. We perform a detailed physicochemical characterization of the nanoalloys and compare their Ag+ ion release with that of pure Ag nanoparticles. Despite a lower released Ag+ ion concentration at pH 7.4, the antibiofilm activity against Escherichia coli (a bacterium known to produce acidic pH environments) is comparable to a pure nanosilver sample with a similar Ag-content. Finally, biocompatibility studies with mouse pre-osteoblasts reveal a decreased cytotoxicity for the alloy coatings and nanoparticles.