Thermo-Sensitive Nanoparticle-Hydrogel Composite Based on Pluronic F127 and Phycocyanin for an Enhanced Chemo-Photodynamic Antitumor Effect

The concurrent utilization of chemotherapy and photodynamic therapy (PDT) can successfully slow the growth of tumors while minimizing systemic toxicity. An injectable temperature-sensitive hydrogel was constructed based on Pluronic F127 and phycocyanin (PC). Nanoparticles formed by self-assembly of doxorubicin and ursolic acid (DOX–UA NPS) were further loaded into the hydrogel to give a local drug delivery platform (DOX–UA NPs@Gel). DOX–UA NPs@Gel can be enriched in situ in tumors and continuously release DOX–UA NPs and free PC. UA can promote the responsiveness of tumor cells to DOX. As a natural photosensitizer, PC can produce reactive oxygen species (ROS) when exposed to laser radiation and has significant PDT activity. The MTT assay demonstrated that DOX–UA NPs@Gel under irradiation caused the highest cytotoxicity at 91.6%. The anti-tumor efficiency of various nanoparticles and nanoparticle-loaded hydrogels (the injection dose of DOX is 6 mg/kg) was verified in the H22 tumor-bearing mice (male ICR). In vivo antitumor results demonstrated that DOX–UA NPs@Gel with the combination of chemotherapy and PDT exhibited unique anticancer efficacy with low toxicity. When exposed to radiation after the experiment, the DOX–UA NPs@Gel showed a tumor volume of merely 319 mm3, displaying an exceptional tumor growth inhibition rate of 91.05%. Therefore, the local drug delivery system based on the thermosensitive hydrogel can effectively achieve synergistic antitumor effects.