School of Chemistry and Chemical Technology, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Biomacromolecules. 2013 May 13;14(5):1627-36. doi: 10.1021/bm4002574. Epub 2013 Apr 2.
Chemotherapy is an important modality in cancer treatment. The major challenge of recent works in this research field is to develop new types of smart nanocarriers that can respond selectively to cancer cell-specific conditions and realize rapid drug release in target cells. In the present study, a reactive oxygen species-responsive nanocarrier has been successfully self-assembled from an amphiphilic hyperbranched polymer consisting of alternative hydrophobic selenide groups and hydrophilic phosphate segments in the dendritic backbone. Because the hydrophobic selenide groups transformed into the hydrophilic selenone groups after oxidation under the exclusive oxidative microenvironment within cancer cells, the amphiphilic hyperbranched precursors become hydrophilic ones. As a result, the nanocarriers were rapidly disassembled in target cells, resulting in fast intracellular drug release. The hydrophilic products of oxidation can be degraded into harmless small molecular species via the enzymatic digestion of the phosphate segments and then eliminated by renal excretion. Meanwhile, the reactive selenium-containing nanocarrier possesses a potent intrinsic anticancer effect since selenium compounds can produce antitumor metabolites which induce apoptosis of cancer cells efficiently. Therefore, this type of therapeutic nanocarriers with a unique drug release mechanism based on an amphiphilic-to-hydrophilic transition provides a new platform for targeted drug delivery and combined therapy.
化疗是癌症治疗的一种重要手段。该研究领域近期的主要挑战是开发新型智能纳米载体，使其能选择性地响应癌细胞特有的条件，并在靶细胞中实现快速药物释放。在本研究中，通过在树枝状主链上交替排列疏水性硒化物基团和亲水性磷酸酯段，成功地自组装了一种对活性氧（ROS）响应的两亲性超支化聚合物纳米载体。由于在癌细胞内特有的氧化微环境下，疏水性硒化物基团在氧化后转化为亲水性硒酮基团，因此两亲性超支化前体变得亲水。结果，纳米载体在靶细胞中迅速解体，导致细胞内药物快速释放。氧化的亲水产物可以通过磷酸酯段的酶解降解成无害的小分子物质，然后通过肾脏排泄消除。同时，含有反应性硒的纳米载体具有潜在的抗癌作用，因为硒化合物可以产生有效的抗肿瘤代谢物，诱导癌细胞凋亡。因此，这种基于两亲性到亲水性转变的独特药物释放机制的治疗性纳米载体为靶向药物输送和联合治疗提供了新的平台。
