Thermo-Sensitive Nanoparticle-Hydrogel Composite Based on Pluronic F127 and Phycocyanin for an Enhanced Chemo-Photodynamic Antitumor Effect
Jinping Song, Rongjian Hu, Jingwen Zhang, Yiyao Yu, Ying Zhou, Wenwen Ding, Xin Wang, Rupei Tang
Abstract
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 mm 3, 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.