Immunotherapeutic Hydrogel with Photothermal Induced Immunogenic Cell Death and STING Activation for Post- Surgical Treatment

摘要

Post-surgical tumor recurrence remains a major clinical concern for patientswith malignant solid tumors. Herein, an immunotherapeutic hydrogel (SAPBA/ZMC/ICG) is developed by incorporating metal ion-cyclic dinucleotide (CDN)nanoparticles (Zn-Mn-CDN, ZMC) and a photosensitizer (indocyanine green,ICG) into phenylboronic acid (PBA)-conjugated sodium alginate (SA_(PBA)) forphotothermal therapy (PTT)-triggered in situ vaccination to inhibit post-surgicalrecurrence and metastasis of malignant tumors. The gelation of SA_(PBA)/ZMC/ICG in the residual tumors can achieve accurate local PTT and the localsustained release of CDN and Mn~（2+） with minimal detrimental off-target toxiceffects. Furthermore, CDN, which is an agonist of the stimulator of interferongenes (STING), along with Mn~（2+） can activate the STING pathway and triggertype-Ⅰ-IFN-driven immune responses against tumors. Therefore, the immunotherapeutichydrogel with enhanced immune response by STING agonistand PTT-induced immunogenic cell death (ICD) reprograms the post-surgicalimmunosuppressive microenvironment, substantially decreasing the postsurgicalrecurrence and metastasis of solid tumors in multiple murine tumormodels when administered during surgical resection. Taken together, PTTtriggeredand STING-mediated in situ cancer vaccination is an effective therapeuticintervention for post-surgical recurrence and metastasis of tumors.