Anaerobic bacteria mediated ‘smart missile’ targeting tumor hypoxic area enhances the therapeutic outcome of lung cancer

In this study, a novel drug delivery strategy is designed by using anaerobic Bifidobacterium infantis as the pre-seeded targets in hypoxic regions of tumor, which enriched the bacterial antibody decorated ‘smart missiles’ in tumor tissues. The intelligent missile showed excellent antitumor effect by releasing therapeutic drugs in response to reductive tumor microenvironment. The strategy shows great application prospects in the treatment of malignant solid tumors. • Bifidobacterium infantis is used as colonized targets to guide drug delivery. • The DOX-NPs are delivered through the binding of B. infantis and its antibodies. • The nanoparticles intelligently release DOX to improve the treatment outcomes. Tumor hypoxia is associated with a negative impact on the clinical treatment of lung cancer. Traditional therapeutic agents cannot be efficiently transported to tumor tissues, resulting in a reduced efficacy and serious toxic side effects. Therefore, the aim of this study is to propose a novel drug delivery strategy to solve this problem. The anaerobic Bifidobacterium infantis ( B. infantis , Bi) is implanted in the hypoxic area of the tumor as the pre-implanted target. The bacterial antibody decorated nano-drug missile (Ab-DOX-s-s-NPS) actively targets the interior of tumor tissue, and enriches therapeutic drug doxorubicin into tumor hypoxic area through bacterial recruitment. The study confirms that the increased concentration of Ab-DOX-s-s-NPS in tumor tissues through the recruitment of B. infantis plays an excellent anti-tumor effect, while the systemic side effects are significantly reduced, suggesting the good therapeutic effect of the B. infantis -mediated drug delivery strategy against lung cancer. Therefore, this work provides an elegant platform for the in vivo delivery of chemotherapeutic drugs to the hypoxic area of the tumor, representing a novel strategy potentially effective in the treatment of solid tumors.