A designed nanomedicine reprogrammes the phenotype and enhances the phagocytic ability of macrophages to ameliorate lung cancer in a mouse model

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide, and its survival rate is less than 15% even after treatment, therefore novel therapeutic strategies are urgently needed. Nowadays, nanomedicine is an emerging and promising strategy for cancer therapy. In this study, we aimed to design a novel nanoparticle to treat lung cancer. Interluekin-4 (IL-4)-stimulated-bone marrow-derived macrophages (BMDMs) were treated with control or three nanoparticles loaded with colony stimulating factor 1 receptor (CSF1R) siRNA (NPsi-CSF1R), signal-regulatory protein alpha (SIRPα) siRNA (NPsi-SIRPα) or equal amounts of CSF1R and SIRPα siRNA (NPsi-CSF1R & si-SIRPα), respectively, then co-cultured with Lewis lung carcinoma (LLC) cells to measure their phagocytosis. In addition, NPsiRNAs were used to treat LLC-implanted mice to evaluate tumor growth. NPsi-CSF1R & si-SIRPα effectively polarized IL-4-stimulated BMDMs (M2-like macrophages) into M1 macrophages and promoted the macrophage-induced phagocytosis of cancer cells. Moreover, NPsi-CSF1R & si-SIRPα significantly reduced the size of tumors in LLC-implanted mice in vivo. NPsi-CSF1R & si-SIRPα showed anti-tumor activity through both reprograming the phenotype of macrophages and promoting the phagocytosis of cancer cells. Our findings revealed that this novel nanoparticle significantly ameliorated lung cancer by regulating the phenotype and proliferation of macrophages, suggesting that CSF1R & SIRPα siRNA-loaded nanoparticles might serve as a promising strategy for lung cancer therapy. Data Availability Statement All datasets generated for this study are included in the manuscript.