葉酸或人類血清蛋白與聚乙二醇及鬼臼毒素複合體藥物的設計、合成及生物活性

Abstract

對於許多人類癌症腫瘤，葉酸是良好的標靶。人類血清白蛋白 (HSA) 可以靶向腫瘤，由於其具有親水性，半衰期長，增強的通透性和滯留性等優點。藥物的聚乙二醇化可以延長循環壽命，穩定和改善治療活性。鬼臼毒素及其衍生物是許多具有藥理活性的化合物。這些組合可能具有增強的抗癌細胞活性。在這裡，我們合成了三種化合物：聚乙二醇-鬼臼毒素、葉酸¬ 聚乙二醇-鬼臼毒素和人類血清白蛋白-聚乙二醇-鬼臼毒素，並比較了這些化合物對癌細胞的細胞毒性。

Folic acid is a great targeting agent for several human cancer types. Human Serum Albumin (HSA) is a hydrophilic protein with long half-life time, which can naturally accumulate in tumor cells due to its permeability and retention effects. PEGylation of a drug can enhance circulation lifetime, stability and improve its therapeutic activity. Considering that podophyllotoxin and its derivatives are pharmacologically active compounds, we then propose that the conjugation of folic acid, HSA and PEG may increase the bioactivity against cancer cells. In this study, we prepared three compounds, which are PEG-Podophyllotoxin, Folate-PEG-Podophyllotoxin, and HSA-PEG-Podophyllotoxin, and assess their cytotoxicity towards triple negative breast cancer.