还原响应性超分子纳米前药的构建及其性能研究
Construction and Property Research of Reduction-Responsive Supramolecular Nanoprodrug
摘要: 基于偶联药物的纳米前药体系能够显著提高载药效率和载药量，还能够避免药物在血液循环过程出现过早泄露的问题，从而降低药物的毒副作用。因此，我们设计并制备了还原响应性的偶联药物IR806-CB，即通过二硫键链接光敏剂IR806和化疗药物苯丁酸氮介CB，该偶联药物IR806-CB与聚乙二醇–环糊精(PEG-CD)通过苯丁酸氮介与环糊精之间的主客体识别作用、π-π堆积作用和亲疏水作用力在水中自组装形成超分子纳米前药SN-IR806/CB。该超分子纳米前药可以通过高通透性和滞留效应有效地富集在肿瘤组织，而后再通过内吞作用进入到肿瘤细胞内，在细胞内的还原环境中，即在高浓度的谷甘光肽(GSH)作用下，二硫键发生断裂，释放出CB。同时，在808 nm的近红外光照射下，IR806不仅能够吸收近红外光转换成热能，使温度升高杀死肿瘤细胞，而且能够释放出活性氧，造成癌细胞的死亡。
Abstract: The nanoprodrug system based on drug-drug conjugation can significantly enhance drug loading efficiency and drug encapsulation, and prevent premature drug leakage in the bloodstream, which reduce the toxic side effects of drugs. Consequently, we designed and synthesized a reduction-re- sponsive drug conjugate IR806-CB by linking the photosensitizer IR806 with the chemotherapeutic agent N-phenylbutyrate CB through a disulfide bond. The conjugated compound IR806-CB self-assembles with polyethylene glycol-cyclodextrin (PEG-CD) in aqueous solution to form supramolecular nanoprodrug SN-IR806/CB via host-guest recognition between N-phenylbutyrate and cyclodextrin, π-π stacking interactions, and hydrophilic-hydrophobic interactions. This supramolecular nanoprodrug can be effectively accumulated in tumor tissues through enhanced permeability and retention effect, subsequently internalized into tumor cells via endocytosis. In the intracellular reducing environment, the disulfide bond could be cleaved under high glutathione (GSH) concentration, leading to the release of CB. Simultaneously, upon irradiation with 808 nm near-infrared light, IR806 not only absorbed near-infrared light for conversion into heat energy that elevated temperature to induce cancer cell death but also generated reactive oxygen species for further cancer cell killing.
文章引用：谢妤, 张宜鑫, 严梓铭, 郑良顺, 丁月. 还原响应性超分子纳米前药的构建及其性能研究[J]. 有机化学研究, 2024, 12(3): 498-504. https://doi.org/10.12677/jocr.2024.123048

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