State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
J Control Release. 2012 Nov 10;163(3):304-14. doi: 10.1016/j.jconrel.2012.06.004. Epub 2012 Jun 12.
An oxaliplatin pro-drug (Oxa(IV)-COOH) with an axial carboxyl group was synthesized and conjugated to biodegradable polymers with pendant hydroxyl groups to prepare polymer-Oxa(IV) conjugates. A hydrophobic anthracycline-based drug, daunorubicin (DRB) was conjugated to similar biodegradable polymers with carboxyl groups to synthesize polymer-DRB conjugates. The two drug conjugates have the similar polymer backbone and are amphiphilic; thus, they can co-assemble into composite micelles. In the composite micelles, the polymer-Oxa(IV) conjugates can release clinically widely used water soluble anticancer drug oxaliplatin (Oxa(II)) upon reduction, while polymer-DRB conjugate is thought to release DRB via acid hydrolysis in the cancer cells. In this way, combination of the hydrophilic platinum drug Oxa(II) and hydrophobic drug DRB can be realized by delivering them in one platform. Moreover, the composite micelles showed reduced systematic toxicity and greater synergistic effect than combination of small molecules of the two anticancer drugs both in vitro and in vivo; thus, this polymer based combination therapy can be useful in future clinic application.
一种具有轴向羧基的奥沙利铂前药（Oxa(IV)-COOH）与具有侧羟基的可生物降解聚合物缀合，制备聚合物-Oxa(IV)缀合物。将疏水性蒽环类药物柔红霉素（DRB）与具有羧基的类似可生物降解聚合物缀合，合成聚合物-DRB 缀合物。这两种药物缀合物具有相似的聚合物主链，且具有两亲性；因此，它们可以共组装成复合胶束。在复合胶束中，聚合物-Oxa(IV)缀合物在还原时可以释放临床上广泛使用的水溶性抗癌药物奥沙利铂（Oxa(II)），而聚合物-DRB 缀合物则被认为可以通过癌细胞中的酸水解释放 DRB。通过将亲水性铂药物 Oxa(II)和疏水性药物 DRB 递送至同一平台，可实现两者的联合用药。此外，与两种抗癌药物的小分子组合相比，该复合胶束在体外和体内均表现出较低的系统毒性和更强的协同作用；因此，这种基于聚合物的联合治疗在未来的临床应用中可能会很有用。
