Dual‐Modal Phototherapeutic Nanoagents Eradicating Drug‐Resistant Bacteria via Multi‐Pathway of Membrane Disruption, Oxidative Damage, and Energy Metabolism Interference

Nanosystem-Mediated Phototherapy (PDT/PTT) - Chemodynamic Therapy for Synergistic Antitumor Therapy: Strategies and Advances

This review constructs a refined mechanistic framework to elaborate the complementary mechanisms of PDT and PTT toward CDT in terms of reaction kinetics modulation, endogenous substrate replenishment, and tumor antioxidant defense inhibition, and the key bottlenecks hindering clinical translation.

Ga-porphyrin MOF-based theranostic platform for methicillin-resistant Staphylococcus aureus: integrated photodynamic and ion-interference antibacterial mechanisms with multimodal readouts

Multifunctional MoO3-X Nanozyme-Hydrogel for Synergistic Photothermal Antibacterial Therapy and Enhanced Healing of Wounds Infected with Drug‑Resistant Bacteria.

This work demonstrates a safe and effective strategy for combating MDR infections through the combined action of photothermal therapy and nanozyme catalysis, offering promising potential for clinical wound management.

NIR‐Triggered On‐Demand Synergistic Therapy for Multidrug‐Resistant Bacterial Infections Via a Smart Phase‐Transition Hydrogel

The rise of multidrug‐resistant bacterial infections and biofilms poses a significant challenge to wound healing. Herein, we developed a temperature‐responsive gel–sol phase‐transition multifunctional hydrogel, named CPAM/GS, by incorporating a novel nanozyme, CeO2@PtAu@Mn2(CO)10, into a gelatin/sodium alginate matrix. The synthesized CeO2@PtAu@Mn2(CO)10 nanozyme exhibits multi‐enzyme activities, including peroxidase‐, oxidase‐, and catalase‐like properties, enabling it to generate ROS in response to the pH of the infected microenvironment and supply oxygen under hypoxic conditions. The CPAM/GS hydrogel demonstrates excellent photothermal performance (η = 47.99%) and allows on‐demand release of carbon monoxide (CO) and nanozymes upon NIR irradiation. In vitro experiments confirmed its potent antibacterial efficacy against methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa through the synergistic effects of photothermal therapy, chemodynamic therapy, and CO gas therapy, achieving a 100% and 99.8% antibacterial rate under NIR irradiation. Furthermore, this hydrogel effectively disrupts preformed biofilms, suppresses virulence gene expression, and promotes cell migration. In a mouse model of MRSA‐infected wounds, treatment with CPAM/GS hydrogel‐NIR(+) significantly accelerated wound healing, eliminated bacteria, and modulated wound microenvironment by reducing pro‐inflammatory cytokines and promoting angiogenesis. Its excellent biosafety and hemostatic performance were also confirmed. This work proposes a multifunctional synergistic strategy for treating multidrug‐resistant bacterial infections and promoting wound regeneration.

Multi-omics decodes a defect-interface dual-engineered PtPb@SbO3-x nanozyme for NIR-II photothermal-amplified eradication of drug-resistant pneumonia

Managing pneumonia caused by multidrug-resistant (MDR) bacteria presents significant clinical challenges. The near-infrared II (NIR-II) laser irradiance exhibits strong photothermal conversion capabilities, making it a promising candidate for photothermal and chemodynamic therapies as non-antibiotic strategies. However, traditional methods are often hindered by issues such as the uncontrollable production of reactive oxygen species and the low efficiency associated with NIR-II photothermal therapy. This underscores the necessity for precisely regulated and highly effective synergistic therapies. To address these limitations, we have innovatively developed a defect/interface dual-engineered nanozyme (PtPb@SbO3-x) and comprehensively characterized its atomic-scale structure and catalytic mechanisms using density functional theory calculations and synchrotron radiation techniques. In vitro experiments demonstrated that PtPb@SbO3-x could efficiently eliminate drug-resistant bacteria and disrupt biofilm structures under low-concentration hydrogen peroxide and NIR-II irradiation while exhibiting excellent biocompatibility. In pneumonia models, the nanozyme enabled rapid infection clearance and significantly reduced inflammatory responses via synergistic photothermal and chemodynamic therapy effects. Furthermore, integrated multi-omics analyses-including metabolomics, transcriptomics, and proteomics-systematically uncovered the molecular mechanisms driving its therapeutic efficacy. This study successfully establishes a non-antibiotic nanozyme-based therapeutic strategy that is efficient, low in toxicity, and non-invasive for treating MDR bacterial infections. It also provides a solid theoretical basis and technical framework for the rational design of defect/interface dual-engineered nanoplatforms.

Dual-metallic porphyrinic MOFs with pH/ROS-responsive release for antibacterial and antioxidant therapy of diabetic infected wounds

Rationale : Chronic diabetic wounds are complicated by multidrug-resistant (MDR) infections and a deleterious oxidative microenvironment, rendering single-target therapies ineffective. This study aimed to develop a smart, dual-metal-organic framework (MOF) nanoplatform (PCNZnCy) capable of microenvironment-responsive, coordinated antibacterial, antioxidant, and pro-regenerative therapy for infected diabetic wounds. Methods : The nanoplatform PCNZnCy was constructed by integrating the natural flavonoid chrysin into a zinc-doped porphyrinic MOF (PCN-224), enabling pH-and reactive oxygen species (ROS)-triggered co-release of Zn² ⁺ and chrysin. Antibacterial and anti-biofilm activity was assessed against biofilm-embedded MDR pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA). Antioxidant and signaling effects were evaluated by measuring ROS scavenging, mitochondrial function, endothelial cell proliferation, and activation of Nrf2/HO-1, STAT3, and Akt pathways, with confirmation using the Nrf2 inhibitor ML385. To assess efficacy and safety in a clinically meaningful setting, we used a diabetic murine wound model infected with P. aeruginosa and a systems-level transcriptomic analysis to capture the broader tissue response. Results : We found that PCNZnCy showed strong synergistic antibacterial activity against MRSA and PA. Beyond that, it scavenged excess ROS, triggered Nrf2/HO-1 signaling, modulated STAT3 and Akt signaling, preserved mitochondrial health, and spurred endothelial cell growth. In diabetic mice, wounds healed faster, with improved collagen deposition and increased formation of new blood vessels, while the compound remained safe. RNA-seq data underscored a decisive move from pro-inflammatory to pro-regenerative gene expression. Conclusions : PCNZnCy adapts to the wound's specific microenvironment, enabling it to kill bacteria, reduce oxidative stress, and promote tissue regeneration. In the infected diabetic models, it worked consistently well. This makes it a strong candidate for multifactorial, complex wound pathologies, in which multiple complications overlap.