Enhanced immunotherapy based on the synergistic click reaction-mediated chemotherapy and photothermal therapy for efficient tumor inhibition

The development of functional materials for the tumor immunogenicity enhancement is desirable for overcoming the low therapeutic efficiency and easy metastasis during tumor treatments. Herein, thermos-responsive nanoparticles composed of photothermal agent (PTA) and click reactive reagent are developed for enhanced immunotherapy application. A metal-bis(dithiolene)-containing PTA with intense near-infrared (NIR) absorption and efficient photo-thermal conversion is developed for thermal-responsive nanoparticles construction. The generated heat by encapsulated PTA will further induce the phase transition of thermos-responsive nanoparticles with the release of chemotherapy reagent to react with the amino groups on functional proteins, realizing PTT and chemotherapy simultaneously. Moreover, immunogenic cell death (ICD) of cancer cells evoked by PTT will be further enhanced by the released reactive reagent. As a result, the synergistic effect of photothermal treatment and reaction-mediated chemotherapy can suppress the growth of primary tumor, and the evoked ICD will further activate the immune response with the suppression of distant tumor. This synergistic treatment strategy provides a reliable and promising approach for cancer immunotherapy in clinic.