Oxygen-Generating Hydrogels Overcome Tumor Hypoxia to Enhance Photodynamic/Gas Synergistic Therapy
2022
Zhang, Mi | Liu, Xiaoguang | Mao, Yinghua | He, Yuhang | Xu, Juan | Zheng, Feng | Tan, Weilong | Rong, Shu | Chen, Yonghong | Jia, Xuemei | Li, Hong
Hypoxic environment is a bottleneck of photodynamic therapy (PDT) in tumor treatment, as oxygen is the critical substrate for photosensitivity reaction. Herein, a sustained oxygen supply system based on cerium nanoparticles and hydrogel (GHCAC) was explored for enhanced synergistic PDT and gas therapy. Ceria nanoparticles were prepared as a drug carrier by self-assembly mediated by hyaluronic acid (HA), a targeting for CD44 on cervical cancer cells, followed by photosensitizer and l-arginine (l-Arg) loading. Then, the GHCAC system was developed by incorporating a prepared nanocarrier (HCePA) and O₂-evolving agent calcium peroxide (CaO₂) into the hydrogel (Gel) developed by a poloxamer. Gel in the system could moderately infiltrate H₂O to react with CaO₂ and generate sustained oxygen using the catalase-like activity of HCePA. The system could efficiently alleviate hypoxia in tumor environments for up to 7 days, meeting the “once injection, repeat irradiation” strategy and enhanced PDT efficacy. Besides, the generated singlet oxygen (¹O₂) in the PDT process could also oxidize l-Arg into high concentrations of nitric oxide for synergistic gas therapy. The developed oxygen supplied and drug delivery Gel system is a new strategy for synergistic PDT/gas therapy to overcome cervical cancer.
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