Cordyceps sinensis Polysaccharide Loaded on Black Phosphorus for Synergistic Immunotherapy and Photothermal Therapy of Cancer

Cordyceps sinensis is a valuable Chinese medicine, possessing multiple bioactive compounds with diverse pharmacological effects. The extracts of C. sinensis, especially the polysaccharide fraction, can suppress the proliferation of different tumor cells, induce apoptosis, and stimulate antitumor immune responses. However, C. sinensis polysaccharides (CSP) have yet to be characterized, with a rare reporting of their effective doses. Immunotherapy depends on harnessing the inherent ability of the immune system to recognize and eliminate tumor cells. Polarizing the anti-inflammatory M2 tumor-associated macrophages (TAMs) to the pro-inflammatory M1 phenotype is an effective antitumor immunotherapy strategy. We designed a drug delivery system with black phosphorus (BP) nanosheets loaded with CSP for synergistic antitumor photothermal therapy (PTT) and immunotherapy. The BP/CSP@PDA-PEG-FA nanoparticles (NPs) enhanced the polarization of M2 macrophages to the M1 phenotype in vitro and in vivo. Moreover, the NPs inhibited the growth of 4T1 xenografts upon near-infrared (NIR) laser stimulation by causing photothermal ablation of tumor cells and promoting T cell-mediated antitumor immune responses. Therefore, BP/CSP@PDA-PEG-FA NPs are a promising platform for combined PTT and immunotherapy for breast tumors.