Here, we propose a light-activated reactive oxygen species (ROS)-responsive nanoplatform that can boost immunogenic cell death (ICD) to release “eat me” signals, and improve CD47-blocking immunotherapy by tumor-targeted co-delivery of photosensitizer IR820 and anti-CD47 antibody (αCD47). Human serum albumin and αCD47 were first constructed into a single nanoparticle using ROS-responsive linkers, which were further conjugated with photosensitizer IR820 via a matrix metalloproteinase-sensitive peptide as linker and then modified with poly(ethylene glycol) on the surface of the obtained nanoparticles. When exposed to the first wave of near infrared (NIR) laser irradiation, the obtained nanoplatform (M-IR820/αCD47@NP) could generate ROS, which triggered nanoparticles dissociation and thus, facilitated the release of αCD47 and IR820. The second wave of NIR laser irradiation was subsequently used to perform phototherapy and induce ICD of tumor cells. An in vitro cellular study showed that M-IR820/αCD47@NP could stimulate dendritic cells activation while simultaneously enhancing the phagocytic activity of macrophage against tumor cells. In 4T1 tumor-bearing mice, M-IR820/αCD47@NP-mediated combination of phototherapy and CD47 blockade could effectively induce the synergistical antitumor immune responses to inhibit the growth of tumors and prevent local tumor recurrence. This work offers a promising strategy to improve the CD47-blocking immunotherapy efficacy using αCD47 nanomedicine.

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