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| 用于黑色素瘤治疗的新型光敏剂药物的研究 |
| Research of the novel photosensitizer for the melanoma therapy |
| 投稿时间：2022-03-14 |
| DOI：10.3969/j.issn.1005-5630.2023.001.007 |
| 中文关键词: 光动力治疗 光敏剂 活性氧 去甲基化 细胞焦亡 |
| 英文关键词:photodynamic therapy photosensitizer reactive oxygen species demethylation pyroptosis |
| 基金项目:上海市军民融合发展专项资金科技创新支持项目(2020-jmrh-kj8) |
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| 中文摘要: |
| 光动力治疗（photodynamic therapy，PDT）一直是黑色素瘤治疗领域的主要方法，而研发更为高效的光敏剂是改进治疗的关键所在。为了提高光动力治疗的效果，设计了一种新型的光敏剂药物，其以传统的光敏剂原卟啉IX（Protoporphyrin IX，PpIX）为基底材料，通过所合成的PMHC18-mPEG将去甲基化药物SGI-1027和PpIX包裹起来形成SGI@ PpIX-mPEG复合体系。PpIX受到光照之后会导致细胞产生大量活性氧（reactive oxygen species， ROS），从而使下游的Caspase-3蛋白含量增加，同时去甲基化药物会上调GSDME蛋白的含量。研究结果表明，所合成的新型光敏剂药物不仅能够产生活性氧杀死癌细胞，而且能够通过Caspase-3蛋白和GSDME蛋白的相互作用进一步导致细胞焦亡从而提升光动力治疗的效果。 |
| 英文摘要: |
| The main method for melanoma is photodynamic therapy (PDT), and the design of more efficient photosensitizers is the key point to melanoma therapy. To promote the therapeutic effect of PDT, a novel photosensitizer was designed. The substrate was the Protoporphyrin IX (PpIX), then the demethylated drug SGI-1027 and PpIX were encapsulated by the synthesized PMHC18-mPEG to form the SGI@PpIX-mPEG complex system. PpIX exposed to illumination causes cells to produce a large amount of reactive oxygen species (ROS), which would increase the content of the downstream protein Caspase-3. The demethylated drug increases the content of GSDME. Research indicates that the synthesized novel photosensitizer drug can not only generate reactive oxygen species to kill cancer cells, but also further lead to pyroptosis and enhance the effect of photodynamic therapy through the interaction between Caspase-3 and GSDME. |
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