Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, P. R. China.
Macromol Biosci. 2017 Oct;17(10). doi: 10.1002/mabi.201600518. Epub 2017 May 2.
Nano-prodrugs usually involve a multistep synthesis which largely compromises their benefits. Here, a smart nano-prodrug platform with reactive drug loading, superb stability, and triggered drug release is reported for targeted melanoma therapy. cRGD-decorated polymersomal mertansine prodrug (cRGD-PS-DM1) is readily fabricated from cRGD-functionalized poly(ethylene glycol)-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate) with simultaneous loading of mertansine (DM1) via thiol-disulfide exchange reaction and disulfide cross-linking of polymersomal membrane. cRGD-PS-DM1 exhibits a size of ≈100 nm, little drug leakage, and fast DM1 release in the presence of 2 × 10 -10 × 10 m glutathione. Tetrazolium-based colorimetric assay (MTT) and confocal microscopy studies confirm effective homing of cRGD-PS-DM1 to α β overexpressing B16F10 melanoma cells. Notably, the in vivo studies show that cRGD-PS-DM1 has a greatly improved toleration as compared with free DM1 and effectively inhibits tumor growth and extends the survival time of B16F10 melanoma-bearing mice. cRGD-PS-DM1 nano-prodrug with reactive drug loading and multifunction provides an advanced nanomedicine for cancer therapy.
纳米前药通常涉及多步合成，这在很大程度上影响了它们的优势。在这里，我们报道了一种具有反应性药物负载、超稳定性和触发药物释放的智能纳米前药平台，用于靶向黑色素瘤治疗。cRGD 修饰的聚合物胶束米托坦前药（cRGD-PS-DM1）可通过巯基-二硫键交换反应和聚合物胶束膜的二硫键交联，从 cRGD 功能化的聚乙二醇-b-聚（三亚甲基碳酸酯-co-二硫代三亚甲基碳酸酯）中轻易制备，同时负载米托坦（DM1）。cRGD-PS-DM1 的粒径约为 100nm，在 2×10 -10 ×10 m 谷胱甘肽存在下，药物泄漏少，DM1 释放迅速。基于四唑的比色法（MTT）和共聚焦显微镜研究证实，cRGD-PS-DM1 能够有效靶向 αβ 过表达的 B16F10 黑色素瘤细胞。值得注意的是，体内研究表明，与游离 DM1 相比，cRGD-PS-DM1 的耐受性大大提高，能够有效抑制肿瘤生长，延长 B16F10 黑色素瘤荷瘤小鼠的存活时间。具有反应性药物负载和多功能的 cRGD-PS-DM1 纳米前药为癌症治疗提供了一种先进的纳米医学。
