A hybrid of lactic acid bacteria and metal-organic frameworks potentiates photodynamic immunotherapy for hypoxia-targeted tumor eradication

Abstract

Development of long-term effective cancer therapy remains a great challenge for both researchers and clinicians. Anaerobic lactic acid bacteria (LAB) possess intrinsic hypoxia tropism to be colonized in tumor niche, and metal-organic frameworks (MOFs) exhibit superior photodynamic responses upon light exposure. However, single treatment of either LAB or MOFs yields unsatisfactory therapeutic outcome. In the present study, an LAB-based drug formulation is prepared to locally generate reactive oxygen species (ROS) in hypoxic tumor and to precisely induce host immunity. These bacteria have been modified by zeolitic imidazolate framework-67 (ZIF-67) and enriched in tumor niche after circulation. The fabricated bacteria facilitate the delivery of ZIF-67 into CT-26 cells, and rapid evolution of ROS is detected after light exposure. The bacterial hybrid induces tumor shrinkage through in vivo photodynamic therapy, and tumor-restricted inflammation attracts both macrophages and T cells for subsequent elimination of remaining cancer cells. Our study provides a material-bacteria hybrid platform for both active tumor targeting and long-term cancer self-immunotherapy.