Sustained Antitumor Immunity Based on Persistent Luminescence Nanoparticles for Cancer Immunotherapy

Abstract Immunotherapy holds great promise for cancer treatment. The key to improving the therapeutic effect is to drive the patient's own immune system to produce a strong, effective, and enduring tumor‐specific immune response. Engineered nanoplatforms show promising potential in strengthening antitumor immune responses. However, current nanotherapeutic platforms based on exogenous responses stimulate the immune system only in a transitory and limited manner, which translates into insufficient immune activation and a low therapeutic efficacy. A novel targeted nano‐immunostimulant (ZGS‐Si‐Pc@HA) is fabricated by coupling persistent luminescence nanoparticles with a photosensitizer and hyaluronic acid for sustained immune stimulation upon irradiation with biological window (659 nm) light. ZGS‐Si‐Pc@HA persistently drives reactive oxygen species production to induce immunogenic cell death, causing a durable tumor‐specific immune response. Upon intratumoral injection, ZGS‐Si‐Pc@HA effectively alleviates immune tolerance and promotes T lymphocyte tumor infiltration. Further, ZGS‐Si‐Pc@HA enhances the therapeutic effect of checkpoint blockade immunotherapy, effectively inhibiting bilateral tumor growth and triggering an immunological memory effect. Nano‐immunostimulants not only provide a new way to boost cancer immunotherapy, but also offer a reliable strategy for fighting cancer metastasis and recurrence clinically.