Caina Xu

Diabetic chronic wounds, characterized by persistent inflammation, bacterial infection, and excessive reactive oxygen and nitrogen species (RONS), pose significant clinical challenges. Conventional hydrogels often fail to solve the multifactorial pathology of diabetic wound healing. Herein, a multifunctional hydrogel dressing (OETFn) was developed integrating oxidized dextran (oDex), ε-polylysine (EPL), tannic acid (TA), and Fe3+ to accelerate infected diabetic wound repair synergistically. The hydrogel was rapidly formed via Schiff base bonds (oDex/EPL) and TA-mediated hydrogen/ionic bonds to enhance multiple functions, while TA/Fe3+ coordination enabled NIR-responsive photothermal antibacterial activity. This innovative hydrogel dressing achieved rapid bacterial eradication through synergistic contact sterilization and photothermal antibacterial activity, while preventing thermal injury to adjacent healthy tissues via controlled temperature modulation. Furthermore, the pH-responsive release of TA from the hydrogel exerted dual immunomodulatory and antioxidant functions. Systematic evaluations demonstrated that the hydrogel effectively scavenged RONS, eliminated bacteria, and promoted macrophage polarization to regenerative M2 phenotypes. In the infected diabetic wound model, OETFn hydrogels accelerated tissue regeneration by resolving infection and inflammation, stimulating fibroblast migration. This study presented an innovative multifunctional hydrogel strategy that could simultaneously address infection, oxidative stress, inflammation, and immune microenvironmental disorders, providing a comprehensive solution with clinical translational potential for diabetic wound management.

The five-year survival rate of patients with colorectal cancer (CRC) liver metastasis is less than 30 %, and chemotherapy resistance and metastatic microenvironment remodeling are the current treatment bottlenecks. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) form a “CRCs-CAFs crosstalk” with colorectal cancer cells (CRCs) by secreting dense extracellular matrix (ECM), free fatty acids (FFA), and pro-metastatic factors, driving a vicious cycle of drug resistance and metastasis. During liver metastasis, hepatic stellate cells (HSCs)-derived CAFs (HSC-CAFs) promote tumor metastasis by remodeling the pre-metastatic microenvironment. Based on clinical sample RNA sequencing and mouse single-cell sequencing to reveal ECM signal enrichment and CAFs activation characteristics, we innovatively constructed a nano-delivery system using hyaluronic acid-modified MIL-100 nanoparticles (OEMH NPs) co-loaded with oxaliplatin (OXA) and epigallocatechin gallate (EGCG). This system can target the CRCs-CAFs crosstalk through CD44 receptor: on the one hand, OEMH NPs can inhibit CAFs activation and reduce ECM deposition, improve drug penetration and down-regulate FFA metabolic reprogramming, reverse OXA resistance; on the other hand, OEMH NPs can block the transformation of HSCs to CAFs, down-regulate pro-metastatic factors such as VEGF/IL-11/ANG, induce vascular normalization, and reprogram the pre-metastatic microenvironment. This strategy can simultaneously achieve primary lesion drug sensitization and liver metastasis inhibition, providing a new paradigm for the treatment of advanced colorectal cancer to break through the traditional treatment dilemma through dual reprogramming of metabolism and microenvironment, and has significant clinical translation potential.

Asthma is a chronic disease with typical pathological features such as airflow limitation, airway inflammation and remodeling. Of these, neutrophilic asthma is considered to be the more severe and corticosteroid-resistant subtype of asthma. Increasing evidence suggests that patients with neutrophilic asthma often accompany with dysbiosis of the internal microbiota, where the increased abundance of non-typeable Haemophilus influenzae (NTHi) is closely related to the neutrophilic asthma phenotype. Furthermore, emerging evidence suggests that reactive oxygen species (ROS) are pivotal in the pathogenesis of neutrophilic asthma. In this study, matrix metalloproteinase-9 (MMP-9)-responsive, catalase-loaded nanogels (M-CAT-NGs) were synthesized, which was composed of MMP-9-sensitive peptide (VPMS), arginine-grafted chitosan and maleimide (CS-Arg-Mal), catalase (CAT), sodium citrate (SC) and ε-poly(L-lysine) (ε-PLL). The M-CAT-NGs showed potent antimicrobial effects and exerted excellent therapeutic effects in the presence of MMP-9 by causing VPMS rupture and responsive release of CAT. In vitro experiments revealed that M-CAT-NGs effectively inhibited the proliferation of NTHi, Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli), while also demonstrating the capacity to modulate the inflammatory response induced by lipopolysaccharide (LPS) and hydrogen peroxide (H2O2) stimulation. In vivo experiments demonstrated that nebulized inhalation of M-CAT-NGs was effective in reducing airway hyperresponsiveness (AHR), alleviating inflammation, downregulating the expression level of ROS in the lung tissues, thus enabling the effective management of neutrophilic asthma. Thus, the development of M-CAT-NGs has shown strong potential for the clinical management of neutrophilic asthma by modulating the inflammatory response.

The problem of antimicrobial resistance (AMR) caused by the abuse of antibiotics is becoming serious. The development of antibacterial materials with synergistic efficiency and treatment of deep tissue/organ infections is imminent. Herein, synergistic antibacterial nanoparticles (MPH NPs) are prepared by loading antibacterial peptide polymyxin B (PMB) on Fe‐based MOF (MIL‐100) with hyaluronic acid (HA) modification. MPH NPs exerts antibacterial effects by chemodynamic therapy (CDT) and the release of PMB. MPH NPs have broad‐spectrum antibacterial properties on Gram‐negative bacteria (E. coli, 100%), Gram‐positive bacteria (S. aureus, 98.5 %), and MRSA (98.4%). Importantly, MPH NPs not only promote the healing of infected wounds but also target lungs to accomplish organ infection therapy. Therefore, this study provides a new strategy for designing a synergetic anti‐AMR bacteria system and the function for deep tissue/organ infection therapy in the future.