Journal of Controlled Release最新文献

Diabetic foot ulcers are linked to a high disability rate, with no effective treatment currently available. Addressing infection, reducing oxidative stress, and safely managing chronic inflammation remain major challenges. In this study, a composite hydrogel dressing was developed using natural substances or clinically approved components (dopamine, D-alpha-tocopheryl polyethylene glycol succinate, and rhein). Upon near-infrared laser irradiation, the composite system rapidly heats and solidifies into a gel with photothermal antibacterial properties. Additionally, the decomposition of hydrogen peroxide releases oxygen, alleviating wound hypoxia. The hydrogel exhibited strong bactericidal activity against multiple bacterial strains. Without laser irradiation, the hydrogel effectively scavenged various free radicals and intracellular reactive oxygen species, restoring redox balance. Furthermore, it significantly reduced the expression of inflammatory cytokines, including interleukin-6 and interleukin-1β. In a diabetic mouse wound model infected with S. aureus, the mild photothermal therapy, combined with the antibacterial action of rhein, effectively managed bacterial infections, reduced inflammation, and promoted wound healing. Consequently, the photo-controlled therapeutic approach, offering antibacterial, antioxidant, and anti-inflammatory effects, holds promise for the effective treatment and management of infected diabetic wounds.

Ferroptosis, triggered by membrane lipid peroxidation (LPO) and diminished antioxidants, can be induced by intracellular iron (II, Fe²⁺). However, the role of nitric oxide (NO) in causing Fe²⁺ overload for ferroptosis remains uncertain. This study reveals that NO can stimulate endogenous Fe²⁺ release by upregulating heme oxygenase 1 (HMOX1) expression. Here, ferritin heavy chain (FHC) siRNA and hyaluronic acid (HA)-modified Arg-stabilized zinc peroxide (AZOSH), a non-ferrous-based nanoagent, is synthesized to trigger ferroptosis by inducing intracellular Fe²⁺ overload. AZOSH, a self-catalyzed NO nanocomplex, effectively generates NO through a reaction of self-supplied Arginine (Arg) and hydrogen peroxide (H₂O₂), which promotes glutathione (GSH) consumption to downregulate glutathione peroxidase 4 (GPX4) expression and produces peroxynitrite (ONOO^-) to enhance LPO. Meanwhile, NO promotes endo/lysosomal escape of siRNA by damaging membrane structures. Moreover, AZOSH significantly triggers Fe²⁺ overload through the synergistic effects of NO-activated HMOX1 expression and FHC siRNA-mediated ferritin sequestration. Additionally, the released Zn²⁺ from AZOSH induces oxidative stress by inhibiting mitochondrial function, further promoting ferroptosis. Consequently, AZOSH-mediated ferroptosis exhibits a strong cellular immunogenic response for T-cell activation and infiltration. Importantly, the integration of AZOSH with an anti-PD-1 antibody results in notable antitumor efficacy in vivo. Therefore, this study provides a novel concept of NO-induced ferroptosis, highlighting its role in enhancing PD-1-based immunotherapeutic efficacy.

Bacterial infections have emerged as a major threat to global public health. The effectiveness of traditional antibiotic treatments is waning due to the increasing prevalence of antimicrobial resistance, leading to an urgent demand for alternative antibacterial technologies. In this context, antibacterial nanomaterials have proven to be powerful tools for treating antibiotic-resistant and recurring infections. Targeting nanomaterials not only enable the precise delivery of bactericidal agents but also ensure controlled release at the infection site, thereby reducing potential systemic side effects. This review collates and categorizes nanomaterial-based responsive and precision-targeted antibacterial strategies into three key types: exogenous stimuli-responsive (including light, ultrasound, magnetism), bacterial microenvironment-responsive (such as pH, enzymes, hypoxia), and targeted antibacterial action (involving electrostatic interaction, covalent bonding, receptor-ligand mechanisms). Furthermore, we discuss recent advances, potential mechanisms, and future prospects in responsive and targeted antimicrobial nanomaterials, aiming to provide a comprehensive overview of the field's development and inspire the formulation of novel, precision-targeted antimicrobial strategies.

Hemophilic arthritis (HA) is one of the most pathologically altered joint diseases. Specifically, periodic spontaneous hemorrhage-induced hyperinflammation of the synovium and irreversible destruction of the cartilage are the main mechanisms that profoundly affect the behavioral functioning and quality of life of patients. In this study, we isolated and characterized platelet-rich plasma-derived exosomes (PRP-exo). We performed microRNA (miRNA) sequencing and bioinformatics analysis on these exosomes to identify the most abundant miRNA, miR-451a. Following this, we developed an M@ZIF-8@miR nanotherapeutic system that utilizes nanoscale zeolitic imidazolate framework (ZIF) as a carrier for miRNA delivery, encapsulated within M2 membranes to enhance its anti-inflammatory effects. In vitro and in vivo studies demonstrated that M@ZIF-8@miR significantly reduced pro-inflammatory cytokines, controlled synovial inflammation, and achieved potent therapeutic efficacy by reducing joint damage. We suggest that the ability of M@ZIF-8@miR nanocomposites to inhibit pro-inflammatory cytokines, enhance cellular uptake, and exhibit good endosomal escape properties makes them promising carriers for the efficient delivery of therapeutic nucleic acid drugs. This approach delays joint degeneration and provides a promising combinatorial strategy for HA treatment.