Inflammatory Responsive Functional Ru Nanoparticle Combine Tumor-Associated Macrophages Repolarization Regulation with Phototherapy for Colorectal Cancer Therapy

Abstract

Due to the complexity and heterogeneity of solid tumors, traditional clinical treatments often only achieve limited therapeutic effects. Tumor-associated macrophages (TAMs) play a key role in the development of solid tumors, and the elimination of solid tumors based on the tumor microenvironment has proven to be an effective therapeutic strategy. Here, we successfully developed Ru-based nanoparticles Ru@ICG-BLZ NPs with inflammatory responsive release drug ability, which could repolarize TAMs into M1 macrophages that can significantly kill tumor cells, meanwhile, it combined with phototherapy enhanced the effect of anti-tumor by producing hyperthermia and ROS. Due to the Ru@ICG-BLZ NPs has superior drug (ICG and BLZ-945) loading capacity and sensitive inflammatory response drug release behavior, which enhanced CT26 cells uptake and penetration ability. Furthermore, in vivo experiments showed that Ru@ICG-BLZ NPs can effectively induce the macrophage M1 polarization by up-regulate the expression of M1 markers (iNOS, IL-12) and exert phototherapy to ablate solid tumor, under the combination therapy of M1 macrophage repolarization and phototherapy showed a good effect of anti-cancer. The lower toxicity and excellent anti-tumor ability of Ru@ICG-BLZ NPs can provide new ideas for the clinical transformation of nanomedicine.