Efficient TNBC immunotherapy by dual reprogramming tumor-infiltrating dendritic cells and tumor-associated macrophages with stimulus-responsive miR155 nanocomplexes

In this study, pH/ROS-responsive microRNA-155 (miR155) nanocomplexes (MiR@PCPmP NPs) were developed to reprogram TIDCs and TAMs for efficient TNBC immunotherapy. This nanoplatform was based on a pH/ROS cleavable copolymer of poly(ethylene glycol)-carboxydimethyl maleate-poly(ethyleneimine)-peroxalate ester-poly(ε-caprolactone) grafted with mannose moieties (PEG-CDM-PEI[Man]-ox-PCL) which self-assembled with miRNA to form nanocomplexes. In the tumor microenvironment, the nanocomplexes showed selective cellular uptake by TIDCs and TAMs through PEG detachment and mannose exposure, followed by efficient endosomal escape, cytosolic miR155 release, and the dual-reprogramming of TIDCs and TAMs. Our results showed that MiR@PCPmP NPs significantly improved antitumor immune responses with highly infiltrating CD8+ T cells while restraining immunosuppressive components in 4T1 tumor-bearing mice. Furthermore, the nanoparticles effectively suppressed both primary tumors and pulmonary metastatic nodules without obvious systemic toxicity. This research highlights the potential of dual-reprogramming of TIDCs and TAMs with the miR155 nanocomplexes as a promising strategy for TNBC immunotherapy, with potential for translation to other cancers with a similar microenvironment.PMID:37722648 | DOI:10.1016/j.ijbiomac.2023.126912
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Source Type: research