Engineering magnetotactic micro organism MVs to synergize chemotherapy, ferroptosis and immunotherapy for augmented antitumor remedy


One important impediment to focused most cancers therapies is the immunosuppressive tumor microenvironment, which might facilitate tumor progress and induce resistance to antitumor therapies. Latest research have indicated that remedy mixed with immunotherapy usually yields a greater prognosis than monotherapy. Bacterial membrane vesicles (MVs), nanostructures launched from the membrane of micro organism, can be utilized as pure nanocarriers for drug supply and stimulate an immune response due to their immunogenicity. Impressed by the event of synergistic therapeutic methods, we herein suggest a novel nanovaccine-based platform to realize chemotherapy, ferroptosis remedy, and immunotherapy concurrently. By merely culturing magnetotactic micro organism within the medium with doxorubicin (DOX) after which extracting specialised MVs (BMVs), BMV@DOX, that are membrane vesicles containing iron ions and DOX, had been obtained. We confirmed that in BMV@DOX, the BMV element can stimulate the innate immune system, DOX acts because the chemotherapeutic agent and iron ions will induce ferroptosis. Moreover, BMV@DOX vesicles modified with DSPE-PEG-cRGD peptides (T-BMV@DOX) have minimized systemic toxicity and elevated tumor-specificity. We demonstrated that the sensible MVs-based nanovaccine system not solely confirmed superior efficiency within the remedy of 4T1 breast most cancers but additionally successfully restrained the expansion of drug-resistant MCF-7/ADR tumors in mice. Furthermore, the nanovaccine may abrogate in vivo lung metastasis of tumor cells in a 4T1-Luc cell induced-lung breast most cancers metastasis mannequin. Collectively, the MVs-based nanoplatform affords another promise for surmounting the constraints of monotherapy and will deserve additional examine for software in synergistic most cancers remedy.

Graphical abstract: Engineering magnetotactic bacteria MVs to synergize chemotherapy, ferroptosis and immunotherapy for augmented antitumor therapy

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