Min Lu

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are life-threatening pulmonary disorders with extremely high mortality rates, for which effective and safe therapeutic strategies remain limited. The development of targeted and biocompatible drug delivery systems is urgently needed to control pulmonary inflammatory cascades while minimizing systemic toxicity. Plant-derived extracellular vesicles offer a naturally safe and anti-inflammatory platform for therapeutic delivery. Ginsenoside Rb1 (GRb1), a major bioactive compound from ginseng, possesses potent anti-inflammatory and anti-apoptotic properties, whereas lemon-derived EVs (LEVs) exhibit intrinsic antioxidant and anti-inflammatory effects. Here, we engineered a multifunctional, biocompatible drug delivery platform, GRb1@LEVs-cRGD, in which ginsenoside Rb1 is incorporated into and fused with LEVs to form hybrid bio-nanovesicles, while the vesicle surface is functionalized with cyclic RGD (cRGD) peptides to target integrin αvβ3 highly expressed in inflamed pulmonary tissues, thereby enhancing site-specific delivery. In vitro and in vivo studies confirmed that GRb1@LEVs-cRGD effectively inhibited M1 macrophage polarization, suppressed inflammatory cascades, and preserved epithelial-endothelial integrity. Furthermore, exogenous cholesterol loading improved vesicle stability, maintained the pH gradient, and enhanced the loading efficiency of tigecycline and vancomycin by six-fold. In murine models of bacterial pneumonia induced by carbapenem-resistant Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus, antibiotic-loaded GRb1@LEVs-cRGD efficiently accumulated at infection sites and exhibited synergistic anti-inflammatory and bactericidal effects. Overall, this study demonstrates that GRb1@LEVs-cRGD is a safe, targeted, and multifunctional therapeutic platform with significant potential for ALI/ARDS treatment.

Excessive wound exudate is a critical factor contributing to the impaired healing of chronic diabetic wounds. The hyper-humid environment and high protein content in exudate foster a persistent inflammatory microenvironment and promote bacterial colonization, both of which significantly impede wound repair. Conventional dressings exhibit limited exudate management capacity; once saturated, they remain in direct contact with the wound bed, concentrating proteins and pathogens and thereby increasing the risk of infection. To address these limitations, we developed a Janus bilayer oriented cryogel with self-pumping functionality. The bottom layer, composed of a hydrophobic thermosensitive polymer, features small vertical channels, while the top hydrophilic layer is engineered with aligned macropores to enable high-capacity exudate absorption. This cryogel rapidly absorbs a range of fluids, including PBS, plasma, protein solutions, and bacterial suspensions, with liquid accumulating in the top layer while the bottom layer remains relatively dry, thus maintaining optimal wound hydration. Notably, the two layers exhibit distinct protein adsorption and bacterial adhesion profiles: the bottom layer shows over 65% reduction in adhesion of A. baumannii, E. coli, and MRSA compared to the top layer. Proteomic analysis reveals that the bottom layer adsorbs significantly fewer proteins, primarily immune and antibacterial factors, whereas the top layer sequesters inflammation-associated proteins. In diabetic mouse wound models, this cryogel effectively manages exudate, reduces inflammation, and markedly accelerates wound healing. This novel self-pumping Janus cryogel presents a promising strategy for exudate control and holds significant potential as a therapeutic platform for diabetic and other chronic wounds.

Managing deep, irregular wounds remains challenging due to poor suturability, persistent bleeding‐induced wet environments, and neuropathic pain. Here, we have developed a sprayable dual‐network microgel adhesive (PR) that rapidly covers complex wound geometries, combining strong wet tissue adhesion with sustained ropivacaine release. The sprayable powder format allows PR microgels to penetrate and adhere to irregular wound beds that conventional dressings cannot reach, with uniform particle size ensuring complete wound protection. Notably, PR maintains exceptional wet adhesion (∼40 kPa, over four times stronger than fibrin glue), enabling reliable sealing even under active bleeding conditions where liquid adhesives fail. The spray application simultaneously delivers liposomal ropivacaine, providing sustained analgesia (240 h release) that maintains pain‐free mobility for over 168 h post‐operation in rodent models. This on‐demand sprayable platform addresses key limitations in wound management by integrating instant hemostatic adhesion with prolonged pain relief in a single conformable format, demonstrating significant potential for clinical application.

Osteomyelitis, especially multidrug-resistant cases, remains a formidable clinical challenge due to recurrent infections and antibiotic limitations. Here, we present an injectable GaCu_Van&HA_CHO-BSA hydrogel that self-assembles in situ within the bone marrow cavity—the epicenter of trained immunity—to simultaneously eradicate pathogens, induce innate immune memory, and regenerate bone. The hydrogel captured bacteria, virulence factors, and inflammatory mediators through multivalent interactions with enhanced injectability, biocompatibility, and sustained antigen release, making it ideal for minimally invasive treatment of osteomyelitis-related bone defects. Mechanistically, adsorbed pathogen signatures activated pattern recognition receptors, triggering metabolic reprogramming (elevated succinate/ATP/lactate), HIF-1α stabilization, amplified glycolysis and inflammation (COX2/iNOS/CD86), and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) production—collectively inducing trained immunity with cross-protection against homologous/heterologous reinfection. Furthermore, glycyrrhizic acid promoted bone tissue repair and modulated immune responses. By converging antimicrobial defense, innate immune memory, and tissue repair into a single platform, this work redefines osteomyelitis management and advances immunomodulatory biomaterials for clinical translation.

Hybrid vesicles are increasingly employed as nanocarrier systems for drug delivery owing to their versatile functionalities. This study presents a multifunctional vesicle delivery platform, designated PMB@LNV-SyBV, which integrates anti-inflammatory lemon-derived exosomes and attenuated bacterial vesicles to deliver polymyxin B (PMB). The incorporation of exogenous cholesterol enhances the drug-loading capacity of these vesicles. Antimicrobial assays confirm that PMB@LNV-SyBV effectively targets carbapenem-resistant Gram-negative bacteria. By inheriting pathogen-associated molecular patterns from native bacteria, PMB@LNV-SyBV is efficiently recognized and internalized by neutrophils, enabling it to reach infection sites alongside neutrophil recruitment. Subsequently, the vesicles are released from neutrophils in response to inflammatory stimuli. In infection models involving Klebsiella pneumoniae-induced mouse pneumonia and K. pneumoniae/Escherichia coli-induced mouse bloodstream infections, PMB@LNV-SyBV significantly reduces bacterial load, modulates pro-inflammatory cytokine release, and increases sepsis survival rates. With its high yield and favorable biocompatibility, the multifunctional PMB@LNV-SyBV represents a promising therapeutic platform for the clinical management of carbapenem-resistant bacterial infections.

Phototherapy offers advantages of non-invasiveness, cost-effectiveness, localized treatment, and potential for home-based care across various medical conditions. However, its adoption is hindered by the large size, limited safety, and professional operation requirements of current phototherapeutic devices. Unlike bulky laser phototherapeutic devices, wearable and implantable LED-based devices overcome these limitations, offering improved safety, portability, and uniform light distribution, making them promising prototypes for next-generation phototherapies. This review explores the home-care potentials of phototherapy from a clinical application perspective and provides a comprehensive overview of its therapeutic mechanisms and diverse applications. By synthesizing the latest advancements and cutting-edge research, we identify key clinical challenges associated with wearable and implantable phototherapy devices and propose fundamental strategies to address these limitations, such as miniaturization, biocompatibility, and energy efficiency. Furthermore, we draw on interdisciplinary cutting-edge research to address the challenges faced by phototherapy devices. We also emphasize the critical value of integrating artificial intelligence (AI) and flexible sensing technologies within phototherapy systems. Specific methods and potential applications are discussed for effectively integrating phototherapy systems with AI algorithms to establish a closed-loop diagnostic and therapeutic system. Grounded in clinical applications, we outline concrete research directions for developing next-generation LED-based phototherapy devices. This review delivers valuable insights for clinicians leveraging phototherapy and offers a roadmap for researchers in material science, flexible electronics, and AI, fostering interdisciplinary innovations to advance future phototherapy applications.