Supramolecularly Engineered Conjugate of Bacteria and Cell Membrane-Coated Magnetic Nanoparticles for Enhanced Ferroptosis and Immunotherapy of Tumors.

Although various ferroptosis inducers including magnetic nanoparticles (Fe 3 O 4 ) and iron-organic frameworks have been applied in cancer treatment, the mild immunogenicity, low targeting efficiency to the tumor, and poor tissue penetration have limited the therapeutic efficacy. Herein, a supramolecularly engineered conjugate between living bacteria (facultative anaerobic Salmonella typhimurium VNP20009, VNP) and cancer cell membranes-coated Fe 3 O 4 nanoparticles is developed for improving targeted delivery of Fe 3 O 4 nanoparticles into the tumor tissue and for synergistic ferroptosis and immunotherapy of tumor. The enhanced ferroptosis induced by both Fe 3 O 4 nanoparticles and the loaded ferroptosis inducing agent (sulfasalazine (SAS)) effectively inhibits tumor growth and generates immune response via immunogenic cell death (ICD). The colonization of VNP in tumors also induces adaptive immune responses and further promotes ferroptosis. Fundamentally, the supramolecular conjugate of VNP and cell membranes-coated Fe 3 O 4 can potentiate the therapeutic capability of each other through mutually magnifying the ferroptosis and immunotherapy, resulting in significantly enhanced antitumor effects.