Aug 2026· Small· pp.
e75217
· 0 citations· 36 references
Medicine
TL;DR
Hollow copper sulfide nanoparticles with a strong photothermal effect were employed as carriers for the loading of the NO-releasing bioactive molecule S-nitrosoglycine, which offers an innovative nanotherapeutic strategy for the precise treatment of drug-resistant bacterial infections.
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a severe global clinical threat due to its multi-antibiotic resistance, abundant virulence factors, and complex pathogenic mechanisms. In the present study, hollow copper sulfide (CuS) nanoparticles (NPs) with a strong photothermal effect were employed as carriers for the loading of the NO-releasing bioactive molecule S-nitrosoglycine (GSNO). These NPs were also camouflaged with mouse red blood cell membranes (RBCMs) via extrusion to fabricate CuS-GSNO@RBCM NPs designed to effectively eliminate MRSA and its biofilms. Under 1064 nm near-infrared laser irradiation, CuS NPs had a mild photothermal effect, establishing an in situ catalytic platform that boosted reactive oxygen species (ROS) production. In the acidic infectious microenvironment, the release of copper ions induced GSNO to produce NO for reactive nitrogen species (RNS) generation. The ROS and RNS generated in situ by this system consumed endogenous MRSA glutathione, disrupting redox homeostasis, with the additional presence of copper ion-mediated copper death forming a multi-bactericidal network. The RBCMs also neutralized proteins secreted by MRSA to reduce lung cell injury. In vitro and in vivo experiments were employed to verify the MRSA-elimination efficacy of the proposed system, which offers an innovative nanotherapeutic strategy for the precise treatment of drug-resistant bacterial infections.
The discovery of new antimicrobial medications has not kept up with the evolution of bacterial resistance, and infections with drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), continue to pose a serious threat to global public health. Antimicrobial photodynamic therapy (aPDT), as an alternative strategy, produces reactive oxygen species (ROS) under light activation and kills drug-resistant bacteria through oxidative damage. Nevertheless, conventional photosensitizers (PSs) are limited by aggregation-caused quenching, inadequate bacterial selectivity, and off-target cytotoxicity. Quaternary ammonium salts (QASs) can preferentially accumulate on bacterial membranes through electrostatic interactions and disrupt the bacterial membranes. The quaternary ammonium PS PK4, reported here has a triphenylamine unit that enhances ROS production. Under white light irradiation, PK4 produces abundant ROS that oxidatively damage bacterial membranes, while exhibiting high photostability and minimal dark toxicity. In an MRSA-infected wound model, PK4-mediated phototherapy can reduce inflammation, accelerate wound healing, and enhance collagen deposition without systemic toxicity, providing a promising aPDT strategy for combating drug-resistant bacterial infections.
Yan Zeng, Huijiao Tang, Xinyu Wu et al.· Molecular Pharmaceutics· 0 citations
Pathogenic bacteria represent a serious threat to public health, and antibiotic therapy remains a major approach for combating bacterial infections. However, the increasing prevalence of drug resistance among pathogenic bacteria has greatly compromised treatment efficacy. Although ursolic acid (UA) possesses various biological activities, its therapeutic application is severely restricted by poor solubility. A positively charged iridium oxide aggregated nanoparticle platform (IOA) was prepared, which was designed to function as both a UA delivery vehicle and a phototherapeutic agent. Under 808 nm NIR irradiation, reactive oxygen species (ROS) and heat were produced by IOA. The antibacterial efficacy of IOA@UA against Methicillin‐resistant
Staphylococcus aureus
(MRSA) was greatly enhanced upon NIR irradiation, even at a UA dose of only 20 µg mL
−
1
, a concentration far below the reported minimum inhibitory concentrations (MICs) of
S. aureus
and MRSA, and the survival rate of bacteria was reduced to 58.8%. These results collectively indicate that the combination of UA chemotherapy with IOA‐mediated phototherapy represents an effective strategy against drug‐resistant bacterial infections.
Yanfang Hu, Shengkai Lin, Yangzhou Wang et al.· ChemistrySelect· 0 citations
The growing threat of bacterial adaptive resistance against nanomaterials necessitates an in-depth understanding of the molecular mechanisms underlying nano-bactericidal effects. Carbon quantum dots (CQDs) have emerged as promising functional nanomaterials for bioimaging, biosensing and biomedical detection, whereas high-performance CQDs eliminating drug-resistant bacterial infections remain greatly limited. Herein, quaternized tartaric acid-based carbon quantum dots (TDAQDs) with prominent antibacterial potency and strong ability to restrict bacterial drug resistance were synthesized using tartaric acid and diallyldimethylammonium chloride (DDA). The average particle diameter (1.21 nm), zeta potential measurement (+35.5 mV), and the MIC (at 5 μg/mL for S. aureus and clinical multidrug-resistant MRSA, and 15 μg/mL for E. coli) were the core quantitative physicochemical and biological parameters of TDAQDs. TDAQDs bind to bacteria through electrostatic interaction and induce reactive oxygen species overproduction, which disrupts bacterial membrane structure and triggers massive cytoplasmic leakage. TMT-based quantitative proteomics analysis revealed that TDAQDs markedly disturbed core biological pathways of S. aureus, including ribosome function, RNA degradation and substance metabolism, while suppressing ABC transporter-associated bacterial pathogenic processes. In vivo wound healing quantification illustrated superior therapeutic performance (91.35% and 88.88% for S. aureus and E. coli-infected wounds), confirming prominent infection elimination and accelerated skin regeneration in TDAQDs-treated groups. In vitro and in vivo biosafety tests verified the good biocompatibility of TDAQDs with negligible cytotoxicity to H9C2 cells, erythrocytes and major mouse organs. Collectively, these findings establish TDAQDs as a robust, biocompatible nanoplatform that simultaneously combats drug-resistant bacteria and mitigates resistance evolution, representing a meaningful step toward developing next-generation antimicrobial strategies to address the global crisis of antibiotic failure.
Lina Wu, Xianquan Feng, Yaoran Gao et al.· European journal of medicina...· 0 citations
This work developed a synergistic single-platform strategy for precise regulation of diabetic wound microenvironments, providing a promising therapeutic alternative for refractory diabetic wound treatment.
A dual-functional nanoplatform constructed through the coordination-driven assembly of gallium ions (Ga3+) and polydopamine (PDA) for synergistic photothermal and metabolic antibiofilm therapy provides a promising therapeutic strategy for the management of biofilm-associated infections.
Xinyan Zheng, Jie Chen, Tongtong Yin et al.· Biomacromolecules· 0 citations
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