Dandelion-derived vesicles-laden hydrogel dressings capable of neutralizing Staphylococcus aureus exotoxins for the care of invasive wounds.

Delayed wound healing caused by bacterial infection remains a major challenge in clinical treatment. Exotoxins incorporated in bacterial extracellular vesicles play a key role as the disease-causing virulence factors. Safe and specific antivirulence agents are expected to be developed as an effective anti-bacterial infection strategy, instead of single antibiotic therapy. Plant-derived extracellular vesicle-like nanoparticles have emerged as promising therapeutic agents for skin diseases, but the elucidations of specific mechanisms of action and clinical transformation still need to be advanced. Here, dandelion-derived extracellular vesicle-like nanoparticles (TH-EVNs) are isolated and exert antivirulence activity through specifically binding to Staphylococcus aureus (S. aureus) exotoxins, thereby protecting the host cell from attack. The neutralization of TH-EVNs against exotoxins has considerable binding force and stability, showing complete detoxification effect in vivo. Then gelatin methacryloyl hydrogel is developed as TH-EVNs-loaded dressing for S. aureus exotoxin-invasive wounds. Hydrogel dressings demonstrate good physical and mechanical properties, thus achieving wound retention and controlled release of TH-EVNs, in addition to promoting cell proliferation and migration. In vivo results show accelerated re-epithelialization, promotion of collagen maturity and reduction of inflammation after treatment. Collectively, the developed TH-EVNs-laden hydrogel dressings provide a potential therapeutic approach for S. aureus exotoxin- associated trauma.

Localized Microsphere/Hydrogel for Tumor Immunotherapy of Cardiac Glycoside with Minimal Toxicity.

It has been reported that cardiac glycosides (CGs) commonly used in clinical practice can inhibit tumor growth by inducing immunogenic cell death (ICD), and their positive benefits have been documented in several clinical trials of drug combinations. However, the inherent cardiogenic side effects need to be addressed before CGs can be truly applied in clinical antitumor therapy. In this study, a dual controlled release microsphere/hydrogel platform (OL-M/Gel) was constructed to precisely control the output of oleandrin (OL, one of the representative CGs) in situ in tumors. With the help of this intelligent drug release platform, OL can be released in vitro and in vivo in a sustained and stable manner. The ability of OL to induce ICD and the subsequent antigen presentation and cytotoxic T-cell cascades was first stated, which resulted in potent tumor growth suppression without significant side effects. In addition, the inhibition of autologous tumor recurrence and metastasis by OL-M/Gel was also revealed. This study is expected to break through the inherent bottleneck of CGs and promote their clinical transformation in the field of antitumor treatment.