A self-guidance biological hybrid drug delivery system driven by anaerobes to inhibit the proliferation and metastasis of colon cancer
Huijuan Zhang, Yaping Wang, Mengting Li, Kexuan Cao, Zijun Qi, Ling Zhu, Zhenzhong Zhang, Lin Hou
Abstract
Colorectal cancer is often accompanied by multiple organ metastasis. Anaerobic Bifidobacterium Infantis (BI) bacterial can selectively grow in hypoxic colorectal tumor microenvironment (TME), to own the natural advantage of preferentially colorectal tumor targeting. Herein, a self-guidance biological hybrid drug delivery system (BI-ES-FeAlg/DOX) based on BI was constructed to inhibit the proliferation and metastasis of colon cancer . Results demonstrated that BI-ES-FeAlg/DOX could overcome physical barriers to target and accumulate in colon tumor tissues. Then DOX was released to kill tumor cells along with the phase transition (solid to liquid) of FeAlg hydrogel, due to Fe 3+ was reduced to Fe 2+ by intracellular GSH. Meanwhile, BI-ES selectively colonized into tumors and expressed endostatin (ES) protein to down-regulate VEGF and bFGF expression, exerting anti-angiogenic effect. Moreover, FeAlg catalyzed H 2 O 2 in the local tumor to generate cytotoxic ·OH, further enhancing the antitumor effect. The pharmacodynamic result in AOM/DSS model proved that BI-ES-FeAlg/DOX had the best therapeutic effect, with the final V/V 0 of 2.19 ± 0.57, which was significantly lower than the other groups. Meanwhile, on CT-26 tumor-bearing model, it also showed an outstanding anti-tumor effect with inhibition rate of 82.12% ± 3.08%. In addition, lung metastases decreased significantly in tumor metastasis model after BI-ES-FeAlg/DOX treatment.