Thanou Maya, Duncan Ruth
Centre for Polymer Therapeutics, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3XF, UK.
Curr Opin Investig Drugs. 2003 Jun;4(6):701-9.
Polymer conjugates are becoming established as a new approach towards improved cancer therapy. These water-soluble, hybrid constructs fall into two main categories: polymer-protein conjugates (already available as licensed products), and polymer-drug conjugates (currently in clinical development). Polyethyleneglycol conjugation of proteins is accepted as a means to reduce immunogenicity, prolong plasma half-life and enhance protein stability. Polymer-drug conjugation promotes tumor targeting by the 'enhanced permeation and retention' effect, and at the cellular level, allows lysosomotropic drug delivery. Eleven polymer-drug conjugates have entered clinical development and activity has already been observed in chemotherapy refractory patients. Certain compounds have also demonstrated a marked reduction in drug toxicity.
聚合物偶联物正成为一种改进癌症治疗的新方法。这些水溶性的杂合构建体主要分为两类：聚合物-蛋白质偶联物（已有获批产品）和聚合物-药物偶联物（目前正处于临床开发阶段）。蛋白质的聚乙二醇化被认为是一种降低免疫原性、延长血浆半衰期并增强蛋白质稳定性的方法。聚合物-药物偶联通过“增强渗透与滞留”效应促进肿瘤靶向，并且在细胞水平上实现溶酶体靶向性药物递送。十一种聚合物-药物偶联物已进入临床开发阶段，并且在化疗难治性患者中已观察到活性。某些化合物还显示出药物毒性显著降低。
