CD47-targeted bismuth selenide nanoparticles actualize improved photothermal therapy by increasing macrophage phagocytosis of cancer cells

CD47, a transmembrane protein overexpressed in most tumors, limits macrophage phagocytosis by interacting with macrophage signal-regulated protein alpha (SIRP alpha). In this study, we have developed CD47-targeted bismuth selenide nanoparticles (Ab-PEG-Bi2Se3) that increase phagocytosis of cancer cells by macrophages to actualize improved photothermal therapy (PTT). The functionalized nanoparticles were constructed by conjugating anti-CD47 antibody (Ab) to PEGylated bismuth selenide nanoparticles (PEG-Bi2Se3). The anti-CD47 antibody modified on the nanoparticles enhanced the phagocytic activity of macrophages toward tumor cells by specifically blocking the crosstalk between CD47 and SIRP alpha. Meanwhile, Ab-PEG-Bi2Se3 showed excellent photothermal performance including strong near infrared (NIR) absorbance, high photothermal conversion efficiency and photostability, and exhibited outstanding in vitro PTT effect under NIR laser irradiation. In vivo therapeutic experiments revealed that this CD47-targeted PTT nanoagent, with the assistance of enhanced macrophage phagocytosis, achieved the goal of tumor eradication. Besides, toxicity studies confirmed that Ab-PEG-Bi2Se3 had good biocompatibility. In conclusion, Ab-PEG-Bi2Se3 may serve as an efficient PTT platform in combination with macrophage-mediated immunotherapy to improve antitumor efficacy.