A nanoparticle-based tour de force for enhancing immunogenic cell death elicited by photodynamic therapy

Immunogenic cell death (ICD) involves the release of ATP, which can be destroyed by ectonucleotidases, converting it into immunosuppressive adenosine. Hence, inhibition of such ectonucleotidases is a strategy for enhancing ICD-elicited anticancer immunity. In a recent paper in Science Translational Medicine, Mao et al. report the construction of reactive oxygen-labile nanoparticles that bear two functionalities, namely (i) the capacity to sensitize cancer cells to near-infrared light (NIL) irradiation, hence inducing ICD in the context of photodynamic therapy, and (ii) the peculiarity to respond to NIL by releasing a pharmacological inhibitor of ectonucleotidases, hence enhancing intratumoral concentrations of ATP. In preclinical models, these nanoparticles are highly efficient in inducing anticancer immune responses.