Tumor-Specific Photothermal-Therapy-Assisted Immunomodulation via Multiresponsive Adjuvant Nanoparticles.

Multiresponsive adjuvant nanoparticles (RMmAGL) were fabricated to perform tumor-specific photothermal therapy while regulating the behavior of tumor-associated immune cells for primary tumor eradication and metastasis inhibition. Core-satellite-like RMmAGL had a core of mannose-functionalized mesoporous silica nanoparticles loaded with R837 (R837@MSN-mannose) connected via hydrazone bonds to satellites of glutamine (Glu)- and lysine (Lys)-comodified gold nanoparticles (AuNPs-Glu/Lys). During therapy, the acidic environment in tumor tissue cleaved the hydrazone bonds to release AuNPs-Glu/Lys, which further accumulated in tumor cells. After internalization, photothermal agents (aggregated AuNPs-Glu/Lys) were generated in situ through the intratumoral enzyme-catalyzed reaction between Glu and Lys, resulting in tumor-specific photothermal therapy. The detachment of AuNPs-Glu/Lys also triggered the release of R837, which matured dendritic cells (DCs) via a vaccine-like mechanism along with the tumor-associated antigens generated by photothermal therapy. These matured DCs further activated surrounding T cells for immunotherapy. Moreover, the resulting free MSN-mannose served as an artificial glycocalyx to continuously induce the polarization of tumor-associated macrophages from an immunosuppressive phenotype to an inflammatory phenotype, thus further enhancing immunotherapy. Both in vivo and in vitro experiments demonstrated significant inhibition of malignant tumors after therapy. This article is protected by copyright. All rights reserved.