School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
Int J Pharm. 2020 May 30;582:119331. doi: 10.1016/j.ijpharm.2020.119331. Epub 2020 Apr 11.
The major drawbacks of the cytotoxin like DM1 are the off-target effects. Here, the targeting nanovesicles were developed by synthesizing tocopherol-SS-DM1 and conjugating a pH low insertion peptide (pHLIP) to PEGylated phospholipids, in which tocopherol-SS-DM1 improves the drug loading and is glutathione responsive in the cytoplasm, meanwhile, the pH insertion peptide targets the acidic microenvironment of cancer cells. Besides, these nanovesicles can accumulate at the endoplasmic reticulum and show increased cancer therapeutic effects both in vitro and in vivo. These targeting nanovesicles provide a novel formulation for subcellular organelle targeting, a platform for precisely delivery of cytotoxic DM1 to cancer cells, and an alternative strategy for antibody-drug conjugates (ADCs).
细胞毒素样 DM1 的主要缺点是脱靶效应。在这里，通过合成生育酚-SS-DM1 并将 pH 低插入肽 (pHLIP) 连接到聚乙二醇化磷脂上，制备了靶向纳米囊泡，其中生育酚-SS-DM1 提高了药物载药量，并在细胞质中对谷胱甘肽有响应，同时，pH 插入肽靶向癌细胞的酸性微环境。此外，这些纳米囊泡可以在内质网中积累，并在体外和体内显示出增强的癌症治疗效果。这些靶向纳米囊泡为亚细胞细胞器靶向提供了一种新的制剂，为细胞毒性 DM1 精确递送到癌细胞提供了一个平台，并为抗体药物偶联物 (ADC) 提供了一种替代策略。
