Multidrug-resistant (MDR) bacterial infections are a severe threat to public health owing to their high risk of fatality. Noticeably, the premature degradation and undeveloped imaging ability of antibiotics still remain challenging. Herein, a selenium nanosystem in response to a bacteria-infected microenvironment is proposed as an antibiotic substitute to detect and inhibit methicillin-resistant Staphylococcus aureus (MRSA) with a combined strategy. Using natural red blood cell membrane (RBCM) and bacteria-responsive gelatin nanoparticles (GNPs), the Ru–Se@GNP-RBCM nanosystem was constructed for effective delivery of Ru-complex-modified selenium nanoparticles (Ru–Se NPs). Taking advantage of natural RBCM, the immune system clearance was reduced and exotoxins were neutralized efficiently. GNPs could be degraded by gelatinase in pathogen-infected areas in situ; therefore, Ru–Se NPs were released to destroy the bacteria cells. Ru–Se NPs with intense fluorescence imaging capability could accurately monitor the infection treatment process. Moreover, excellent in vivo bacteria elimination and a facilitated wound healing process were confirmed by two kinds of MRSA-infected mice models. Overall, the above advantages proved that the prepared nanosystem is a promising antibiotic alternative to combat the ever-threatening multidrug-resistant bacteria.

Inducing immunogenic cell death (ICD) that enhances the immunogenicity of dead cancer cells is a new strategy for tumor immunotherapy, but efficiently triggering ICD is the biggest obstacle to achieving this strategy, especially for distant and deep-seated tumors. Here, a new therapeutic system (Pd-Dox@TGMs NPs) that can effectively trigger ICD by combining chemotherapy and photothermal therapy was designed. The nanosystem was fabricated by integrating doxorubicin (Dox) and a photothermal reagent palladium nanoparticles (Pd NPs) into amphiphile triglycerol monostearates (TGMs), which showed specific accumulation, deep penetration, and activation in response to the tumoral enzymatic microenvironment. It was proved that codelivery of Dox and Pd NPs not only effectively killed CT26 cells through chemotherapy and photothermal therapy but also promoted the release of dangerous signaling molecules, such as high mobility group box 1, calreticulin, and adenosine triphosphate, improving the immunogenicity of dead tumor cells. The effective ICD induction mediated by Pd-Dox@TGMs NPs boosted the PD-L1 checkpoint blockade effect, which efficiently improved the infiltration of toxic T lymphocytes at the tumor site and showed excellent tumor treatment effects to both primary and abscopal tumors. Therefore, this work provides a simple and effective immunotherapeutic strategy by combining chemical-photothermal therapy to enhance immune response.

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