posted on 2022-01-13, 16:36authored byLin-Ping Zhao, Rong-Rong Zheng, Ren-Jiang Kong, Chu-Yu Huang, Xiao-Na Rao, Ni Yang, A-Li Chen, Xi-Yong Yu, Hong Cheng, Shi-Ying Li
Abnormal
metabolism of cancer cells results in complex tumor microenvironments
(TME), which play a dominant role in tumor metastasis. Herein, self-delivery
ternary bioregulators (designated as TerBio) are constructed for photodynamic
amplified immunotherapy against colorectal cancer by TME reprogramming.
Specifically, carrier-free TerBio are prepared by the self-assembly
of chlorine e6, SB505124 (SB), and lonidamine (Lon), which exhibit
improved tumor accumulation, tumor penetration, and cellular uptake
behaviors. Interestingly, TerBio-mediated photodynamic therapy (PDT)
could not only inhibit the primary tumor growth but also induce immunogenic
cell death of tumors to activate the cascade immune response. Furthermore,
TerBio are capable of TME reprograming by SB-triggered transforming
growth factor (TGF)-β blockage and Lon-induced lactic acid efflux
inhibition. As a consequence, TerBio significantly suppresses distant
and metastatic tumor growth by PDT-amplified immunotherapy. This study
might advance the development of self-delivery nanomedicine against
malignant tumor growth and metastasis.