Anti-Melanoma Activity of Single Intratumoral Injection of ZnPc Micelles Mixed With in situ Gel in B16 Bearing Mouse

• Published in: Journal of pharmaceutical sciences 2024-02, Vol.113 (2), p.463-470
• Main Authors: Xu, Jing-hua, Zhang, Chun-xue, Cang, Ai-jun, Yan, Ran, Liu, Shi-wen, Liu, Rui, Zou, Nv-jie, Wang, Shao-ning, Xu, Hui, Li, Lin-sen
• Format: Article
• Language: English
• Subjects: Animals; Anti-melanoma; Antineoplastic Agents; Cell Line, Tumor; Gels; Injections, Intralesional; Intratumoral injection; Isoindoles; Melanoma - drug therapy; Mice; Micelles; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - chemistry; Reactive Oxygen Species - metabolism; Thermosensitive gel; Zinc Compounds; ZnPc
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2023.10.020

Photodynamic therapy (PDT) is a potential treatment strategy for melanoma. As a second-generation photosensitizer, Zinc phthalocyanine (ZnPc) has many advantages for anti-tumor PDTs, such as strong absorption in the red and near infrared regions, high photo and chemical stability, etc. However, ZnPc has a poor water solubility and is apt to aggregate due to the π-π interaction between molecules, which limits its applications. In this study, various solvents and surfactants were screened for dissolving ZnPc and preparing ZnPc@SDC-TPGS micelle and thermosensitive in situ gel. After the cytotoxic effects of thermosensitive gels on PDT were tested, the antitumor effects on PDT of them in mice by intratumoral injection were evaluated, including body weight, and tumor weight, volume and morphology. The cell death pathway and the relationship of reactive oxygen species yield with apoptotic rate of tumor cells induced by ZnPc in situ gel were investigated. The results were that N-methyl-pyrrolidone (NMP) mixed with 2 % SDC and aqueous solution containing 2 % TPGS and 2 % SDC were used to synthesize ZnPc@SDC-TPGS micelle and the thermosensitive in situ gel. The cytotoxic effects of thermosensitive gels showed good tumor suppression of ZnPc@SDC-TPGS in situ gel and no toxicity of the blank gel. Intratumoral injection in situ gel containing 3 µg ZnPc under irradiation demonstrated good tumor inhibition in mice with melanoma. Apoptosis has been established as the primary pathway of cell death, and the production of reactive oxygen species (ROS) plays a crucial role in cellular apoptosis induced by ZnPc@SDC-TPGS in situ gel. In conclusion, the intratumoral injection of ZnPc@SDC-TPGS thermosensitive in situ gel provides a promising local treatment option for melanoma.