NIR-light-mediated spatially selective triggering of anti-tumor immunity via upconversion nanoparticle-based immunodevices

摘要

Immunomodulatory therapies are becoming a paradigm-shifting treatment modality for cancer. Despite promising clinical results, cancer immunotherapy is accompanied with off-tumor toxicity and autoimmune adverse effects. Thus, the development of smarter systems to regulate immune responses with superior spatiotemporal precision and enhanced safety is urgently needed. Here we report an activatable engineered immunodevice that enables remote control over the antitumor immunity in vitro and in vivo with near-infrared (NIR) light. The immunodevice is composed of a rationally designed UV light-activatable immunostimulatory agent and upconversion nanoparticle, which acts as a transducer to shift the light sensitivity of the device to the NIR window. The controlled immune regulation allows the generation of effective immune response within tumor without disturbing immunity elsewhere in the body, thereby maintaining the antitumor efficacy while mitigating systemic toxicity. The present work illustrates the potential of the remote-controlled immunodevice for triggering of immunoactivity at the right time and site.