Phagocyte-membrane-coated and laser-responsive nanoparticles control primary and metastatic cancer by inducing anti-tumor immunity

To achieve safe and effective antitumor immunity, we constructed the M1-macrophage-membrane-coated nanoparticles [(C/I)[email protected](D)&M1m] having laser-responsive, size-changeable, on-demand drug release and prolonged circulation retention properties. (C/I)[email protected](D)&M1m delayed clearance by the phagocytic system and homed to tumor efficiently. Upon 650 nm laser irradiation, the hydrophobic core of the PEGylated bilirubin nanoparticles (BP) got disrupted, releasing small-sized deep-penetrating B-A(D) particles, photosensitive chlorin e6 (C), and tolerance-inducing indoleamine 2,3-dioxygenase inhibitor, indoximode (I). Treatment-induced immunogenic cell death and antitumor immunity, suppressing primary tumor growth in both 4T1 and B16F10 models without causing any adverse effects. Most importantly, it inhibited primary tumor recurrence as well as metastasis. Thus, this study provides a promising combinatorial strategy to trigger antitumor immunity in malignancies.