Design of Light‐Activated Nanoplatform through Boosting “Eat Me” Signals for Improved CD47‐Blocking Immunotherapy

Abstract Here, the authors 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 codelivery of photosensitizer IR820 and anti‐CD47 antibody ( α CD47). Human serum albumin and α CD47 are first constructed into a single nanoparticle using ROS‐responsive linkers, which are 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/ α CD47@NP) can generate ROS, which triggers nanoparticles dissociation and thus, facilitates the release of α CD47 and IR820. The second wave of NIR laser irradiation is subsequently used to perform phototherapy and induce ICD of tumor cells. An in vitro cellular study shows that M‐IR820/ α CD47@NP can stimulate dendritic cells activation while simultaneously enhancing the phagocytic activity of macrophage against tumor cells. In 4T1 tumor‐bearing mice, M‐IR820/ α CD47@NP‐mediated combination of phototherapy and CD47 blockade can effectively induce the synergistic 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 α CD47 nanomedicine.