Low-temperature photothermal-chemotherapy enhancing tumor immunotherapy by tetrahedral framework nucleic acids nanogels based drug delivery system

To achieve a balance between antitumor efficacy in photothermal therapy (PTT) and high-temperature (>50℃) induced side effects, a novel tetrahedral framework nucleic acid (FNA) nanogel (FNANG) coated with polydopamine (PDA) (abbreviation: PP-FNANG) was designed to achieve siRNA-mediated low-temperature PTT. First, siRNA targeted heat shock protein 70 (HSP70) was used as crosslinker to guide FNA through nucleic acid hybridization to obtain FNANG, and simultaneously loaded doxorubicin (DOX). The obtained FNANG was coated with PEGylated PDA, which not only protected the FNANG from enzymatic degradation, but also made the FNANG have excellent photothermal conversion ability under near infrared (NIR) irradiation. FNANG realized the effective delivery of siHSP70 and realized the low-temperature photothermal therapy mediated by siRNA. Notably, PP-FNANG combined with its loaded DOX showed excellent synergistic effect, and could effectively induce the immunogenic cell death (ICD), promote the activation and infiltration of T lymphocyte, promote the maturation of dendritic cells and the secretion of related cytokines, and effectively inhibit melanoma. This study provided a simple and effective exploration strategy for new vector design based on FNA and collaborative therapy.