Targeting Hydrogel for Intelligent Recognition and Spatiotemporal Control in Cell-Based Therapeutics

Smart drug platforms based on spatiotemporally controlled release and integration of tumor imaging are expected to overcome the inefficiency and uncertainty of traditional theranostic modes. In this study, a composite consisting of a thermosensitive hydrogel (polyvinyl alcohol-carboxylic acid hydrogel (PCF)) and a multifunctional nanoparticle (Fe₃O₄@Au/Mn(Zn)-4-carboxyphenyl porphyrin/polydopamine (FAM^xP)) is developed to combine tumor immunogenic cell death (ICD)/immune checkpoint blockade (ICB) therapy under the guidance of magnetic resonance imaging (MRI) and fluorescence imaging (FI). It can not only further recognize the target cells through the folate receptor of tumor cells, but also produce thermal dissolution after exposure to near-infrared light to slowly release FAM^xP in situ, thereby prolonging the treatment time and avoiding tumor recurrence. As FAM^xP entered the tumor cells, it released FAM^x in a pH-dependent manner. Chemodynamic, photothermal and photodynamic therapy can cause significant ICD in cancer cells. ICB can thus be further enhanced by injecting anti-programmed cell death ligand 1, improving the effectiveness of tumor treatment. The developed PCF-FAM^xP composite hydrogel may represent an updated drug design approach with simple compositions for cooperative MRI/FI-guided targeted therapeutic pathways for tumors.