Developing an effective dressing against bacterial infection and synchronously addressing wound complications, such as bleeding, long-term inflammation, and reinfection, are highly desirable in clinical practice. In this work, a second near-infrared (NIR-II) responsive nanohybrid consisting of imipenem encapsulated liposome with gold-shell and lipopolysaccharide (LPS)-targeting aptamer, namely ILGA, is constructed for bacteria elimination. Benefiting from the delicate structure, ILGA exhibits strong affinity and a reliable photothermal/antibiotic therapeutic effect toward multidrug-resistant Pseudomonas aeruginosa (MDR-PA). Furthermore, by incorporating ILGA with a thermosensitive hydrogel poly­(lactic-co-glycolic acid)–polyethylene glycol–poly­(lactic-co-glycolic acid) (PLGA-PEG-PLGA), a sprayable dressing ILGA@Gel was prepared, which enables a quick on-demand gelation (10 s) for wound hemostasis and offers excellent photothermal/antibiotic efficacy to sterilize the infected wound. Additionally, ILGA@Gel provides satisfactory wound-healing environments by reeducating wound-associated macrophages for inflammation alleviation and forming a gel layer to block exogenous bacterial reinfection. This biomimetic hydrogel reveals excellent bacteria eradication and wound recovery effectiveness, demonstrating its promising potential for managing complicated infected wounds.

Starvation therapy has been considered a promising strategy in cancer treatment for altering the tumor microenvironment (TME) and causing a cascade of therapeutic effects. However, it is still highly challenging to establish a therapeutic strategy for precisely and potently depriving tumoral nutrition. In this study, a glucose oxidase (GOx) and thrombin-incorporated erythrocyte vesicle (EV) with cyclic (Arg-Gly-Asp) (cRGD) peptide modification, denoted as EV@RGT, were synthesized for precisely depriving tumoral nutrition and sequentially inducing second near-infrared region (NIR-II) photothermal therapy (PTT) and immune activation. The EV@RGT could specifically accumulate at the tumor site and release the enzymes at the acidic TME. The combination of GOx and thrombin exhausts tumoral glucose and blocks the nutrition supply at the same time, resulting in severe energy deficiency and reactive oxygen species (ROS) enrichment within tumor cells. Subsequently, the abundant clotted erythrocytes in tumor vessels present outstanding localized NIR-II PTT for cancer eradication owing to the hemoglobin. Furthermore, the abundant ROS generated by enhanced starvation therapy repolarizes resident macrophages into the antitumor M1 phenotype via a DNA damage-induced STING/NF-κB pathway, ultimately contributing to tumor elimination. Consequently, the engineered EV@RGT demonstrates powerful antitumor efficiency based on precise nutrition deprivation, sequential NIR-II PTT, and immune activation effect. This work provides an effective strategy for the antitumor application of enzyme-based reinforced starvation therapy.

Accumulation of obsolete biomolecules can accelerate cell senescence and organism aging. The two efficient intracellular systems, namely the ubiquitin‐proteasome system and the autophagy‐lysosome system, play important roles in dealing with cellular wastes. However, how multicellular organisms orchestrate the processing of obsolete molecules and delay aging remains unclear. Herein, it is shown that prevention of exosome release by GW4869 or Rab27a−/− accelerated senescence in various cells and mice, while stimulating exosome release by nutrient restriction delays aging. Interestingly, exosomes isolate from serum‐deprived cells or diet‐restricted human plasma, enriched with garbage biomolecules, including misfolded proteins, oxidized lipids, and proteins. These cellular wastes can be englobed by macrophages, eventually, for disintegration in vivo. Inhibition of nutrient‐sensing mTORC1 signaling increases exosome release and delays senescence, while constitutive activation of mTORC1 reduces exosome secretion and exacerbates senescence in vitro and in mice. Notably, inhibition of exosome release attenuates nutrient restriction‐ or rapamycin‐delayed senescence, supporting a key role for exosome secretion in this process. This study reveals a potential mechanism by which stimulated exosome release delays aging in multicellular organisms, by orchestrating the harmful biomolecules disposal via exosomes and macrophages.