Self-Delivery\nTernary Bioregulators for Photodynamic\nAmplified Immunotherapy by Tumor Microenvironment Reprogramming

Abstract

Abnormal\nmetabolism of cancer cells results in complex tumor microenvironments\n(TME), which play a dominant role in tumor metastasis. Herein, self-delivery\nternary bioregulators (designated as TerBio) are constructed for photodynamic\namplified immunotherapy against colorectal cancer by TME reprogramming.\nSpecifically, carrier-free TerBio are prepared by the self-assembly\nof chlorine e6, SB505124 (SB), and lonidamine (Lon), which exhibit\nimproved tumor accumulation, tumor penetration, and cellular uptake\nbehaviors. Interestingly, TerBio-mediated photodynamic therapy (PDT)\ncould not only inhibit the primary tumor growth but also induce immunogenic\ncell death of tumors to activate the cascade immune response. Furthermore,\nTerBio are capable of TME reprograming by SB-triggered transforming\ngrowth factor (TGF)-β blockage and Lon-induced lactic acid efflux\ninhibition. As a consequence, TerBio significantly suppresses distant\nand metastatic tumor growth by PDT-amplified immunotherapy. This study\nmight advance the development of self-delivery nanomedicine against\nmalignant tumor growth and metastasis.