The synthesized ITN Art‐M demonstrates superior MRSA eradication and recurrence prevention, offering a potent, intelligent alternative that may surpass conventional antibiotics in combating bacteria and many other pathogenic cells.
Abstract
The rapid evolution of antibiotic‐resistant bacteria, particularly methicillin‐resistant Staphylococcus aureus (MRSA), poses a critical threat to human healthcare, underscoring the need for antibiotic‐free antibacterial strategies that achieve both effective pathogen eradication and sustained protection against reinfection. Here, inspired by the functions of natural macrophages, we report the de novo design of an Ir/TiN‐based photothermal‐activable artificial macrophage (ITN Art‐M) with enhanced systemic antibacterial activity to combat primary and secondary infections caused by antibiotic‐resistant bacteria. The experimental studies and theoretical calculations reveal that the ITN Art‐M displays spiky topology, robust photothermal properties, and electron‐rich Ir‐Ti catalytic sites for reactive oxygen species (ROS) production, which can efficiently capture and kill antibiotic‐resistant bacteria. Meanwhile, the synthesized ITN Art‐M can induce severe bacterial antigen leakage and exposure through synergistic oxidative and hyperthermic stress, thereby potently stimulating systemic antibacterial responses, assisting in the elimination of primary infections and establishing durable defensive surveillance against secondary infections. Notably, ITN Art‐M demonstrates superior MRSA eradication and recurrence prevention, offering a potent, intelligent alternative that may surpass conventional antibiotics in combating bacteria and many other pathogenic cells.
Bacterial liver abscesses represent a significant threat to human health, and the emergence of infections caused by multidrug-resistant bacteria exacerbates this issue. The urgent need to develop effective antibacterial strategies to overcome antibiotic resistance is well recognized. In this context, we present an aggregation-induced emission (AIE) luminogen (TTQ) exhibiting near-infrared II (NIR-II) luminescence, which facilitates precise imaging-guided photothermal eradication of carbapenem-resistant Klebsiella pneumoniae (CRKP) biofilms and liver abscesses. TTQ exhibited remarkable photothermal conversion efficiency and deep-tissue penetration capabilities, facilitating effective bacterial eradication through irreversible membrane disruption and intracellular disorganization. In vitro investigations demonstrated that TTQ exhibited significant antibacterial activity against CRKP and effectively disrupted biofilms via localized hyperthermia-induced membrane damage. In vivo assessments indicated that TTQ’s rapid hepatic accumulation and extended retention facilitated precise photothermal therapy (PTT) of abscesses induced by CRKP. This treatment resulted in the full resolution of abscesses, a marked reduction in pro-inflammatory cytokines, and enhanced survival rates. The outstanding bactericidal efficacy, deep-tissue therapeutic capability, and biocompatibility of TTQ suggest its potential as a next-generation, nonantibiotic approach for the management of deep-seated multidrug-resistant infections.
Dawei Liang, Jin Zhang, Wenwen Zhan et al.· ACS Applied Nano Materials· 0 citations
Diabetic wounds are difficult to heal due to infections caused by multidrug‐resistant bacteria. Although photodynamic therapy (PDT) and antimicrobial peptides (AMPs) have emerged as promising alternatives, each faces inherent limitations: PDT‐generated reactive oxygen species (ROS) have an extremely short lifespan (10–320 ns) and limited diffusion (10–55 nm), while AMPs are structurally unstable, potentially cytotoxic at high doses, and even induce bacterial resistance. To overcome these drawbacks, we developed a synergistic nanoplatform by integrating the AMP Indolicidin with the photosensitizer PTBT, further encapsulated within a thermosensitive F127 hydrogel (PTBT/I@F127). The system formed uniform, highly photosensitive nanoparticles in which Indolicidin, located on the outer surface, first disrupted bacterial membranes, facilitating the contact of PTBT with bacteria. Subsequently, abundant ROS were generated for rapidly killing bacteria under an 808‐nm laser irradiation, which effectively compensated for the limited diffusion of ROS and reinforced the antibacterial effect of Indolicidin before its degradation. In vitro, PTBT/I@F127 effectively killed methicillin‐resistant Staphylococcus aureus (MRSA) and E. coli with a remarkable synergy. In diabetic mice and pig models, wound healing rates reached 98% and 83%, respectively, with remarkable angiogenesis and collagen deposition, after receiving PTBT/I@F127. Transcriptomic analysis revealed that Wnt/β‐catenin signaling pathways were involved in promoting tissue regeneration, while inflammation‐associated signaling pathways, such as NF‐κB and IL‐17, were concurrently regulated, thereby alleviating inflammation and reshaping the immune microenvironment in infected wounds. Collectively, this PTBT/Indolicidin‐based thermosensitive hydrogel effectively eliminated resistant bacteria, mitigated inflammation, stimulated angiogenesis, and accelerated healing of infected diabetic wounds, offering a safe, controllable, and translationally promising therapeutic strategy.
Xiang Chen, Zhanming Lin, Yongjun Mo et al.· Advances in Materials· 0 citations
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.
Xiangjun Chen, Sai Zhang, Yating Liu et al.· Small· 0 citations
Bacterial pneumonia treatment is severely hampered by escalating antibiotic resistance and physiological drug delivery barriers. To address these critical challenges, we report the development of an intelligent biomimetic Janus nanomotor (MAgAu@CM) featuring a built‐in “electronic lock” for spatiotemporally controlled on‐demand therapy. The nanomotor is constructed from a melanin‐supported AgAu alloy and camouflaged with an erythrocyte and platelet hybrid membrane, ensuring prolonged systemic circulation and active inflammation targeting. Crucially, the potent silver component remains therapeutically inert during circulation due to a highly stable electronic compensation mechanism. Upon near‐infrared irradiation at the target infection site, the localized photothermal effect acts as a specific “key.” This thermal intervention not only provides direct hyperthermic ablation of the pathogens but also disrupts the electronic equilibrium, triggering the burst release of bactericidal Ag
+
for powerful synergistic chemo‐photothermal eradication. Concurrently, this photothermal input overclocks the inherent nanozyme activity of the nanomotor, catalyzing the decomposition of endogenous H
2
O
2
to generate robust oxygen‐driven mechanical propulsion for deep penetration into complex infectious biofilms. Furthermore, this system actively remodels the hostile pathological microenvironment by alleviating local hypoxia and promoting the functional polarization of macrophages toward a tissue‐repairing M2 phenotype. By integrating biomimetic stealth, active navigation, stimuli‐responsive propulsion, and microenvironment remodeling, this multifunctional nanoplatform establishes a highly promising translational paradigm for combating deep‐seated and multidrug‐resistant bacterial infections.
Chenglong Xue, Xiaoyu Zhao, Yuqian Wang et al.· BMEMat· 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
A biomimetic cascade nanoplatform that integrates a photothermal nanozyme core, surface-anchored DNase I-functionalized gold nanoclusters, and a pre-activated macrophage membrane camouflage enables synergistic biofilm eradication and immune microenvironment modulation against drug-resistant infections.
Chang Liao, Jiamei Liao, Xiaolin Nie et al.· RSC Advances· 0 citations