Metal Ions Driven Assembly for Constructing Metal–Phenolic Network Nanoparticles Loaded Hydrogel as Tumor Photothermal-Immunotherapy Agent

Abstract

Developing of fast and eco-friendly one step synthesis method for constructing multifunctional hydrogel to eliminate postoperative residual tumor cells is highly required. In this work, Fe3+ ions were selected as inorganic cross-linker to link with gelatin (Gel) and protocatechuic acid (PA) to drive assembly for forming gelatin-metal-polyphenol (GMP) Gel-Fe-PA hydrogel. The in situ formed metal-phenolic network nanoparticles (MPN NPs) Fe-PA can effectively response to NIR stimulation and then transform light energy into heat energy for inducing tumor cells apoptosis. Meanwhile, the damage associated molecular patterns including adenosine triphosphate (ATP), calreticulin (CRT) and high mobility group box-1 (HMGB1) will release and be captured by dendritic cells (DCs) for subsequently activating the immune response. In vivo local antitumor therapy results showed that GMP hydrogel-mediated photothermal effect could effectively inhibit the tumor tissue growth in residual tumor bed. Additionally, the distant tumor tissue growth could also be inhibited in bilateral 4T1 tumor model. Encouraged by this strategy, metal ions driven assembly between gel and polyphenol may open a novel approach to in situ fabricate MPN NPs loaded hydrogel with advanced tumor photothermal-immunotherapy ability.