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However, conventional combinational strategies mainly focus on the employment of drug carriers to deliver immunomodulators, chemotherapeutics, or their combinations, always suffering from complicated preparation and carrier\u2010relevant side effects. Here, the fabrication of bacterial flagellum\u2010drug nanoconjugates (FDNCs) for carrier\u2010free immunochemotherapy is described. FDNCs are simply prepared by attaching chemotherapeutics to amine residues of flagellin through an acid\u2010sensitive and traceless cis\u2010aconityl linker. By virtue of native nanofibrous structure and immunogenicity, bacterial flagella not only show long\u2010term tumor retention and highly efficient cell internalization, but also provoke robust systemic antitumor immune responses. Meanwhile, conjugated chemotherapeutics exhibit an acid\u2010mediated release profile and durable intratumoral exposure, which can induce potent tumor cell inhibition via direct killing. More importantly, this combination is able to augment immunoactivation effects associated with chemotherapy\u2010enabled immunogenic tumor cell death to further enhance antitumor efficacy. By leveraging the innate response of the immune system to pathogens, the conjugation of therapeutic agents with self\u2010adjuvant bacterial flagella provides an alternative approach to develop carrier\u2010free nanotherapeutics for tumor immunochemotherapy.<\/jats:p>","DOI":"10.1002\/smll.202306303","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:50:49Z","timestamp":1698972649000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bacterial Flagellum\u2013Drug Nanoconjugates for Carrier\u2010Free Immunochemotherapy"],"prefix":"10.1002","volume":"20","author":[{"given":"Zhenzhen","family":"Fu","sequence":"first","affiliation":[{"name":"School of Chemistry and Chemical Engineering Shanghai Jiao Tong University  Shanghai 200240 China"},{"name":"Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine Institute of Molecular Medicine State Key Laboratory of Oncogenes 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