Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
Biomacromolecules. 2012 Aug 13;13(8):2225-8. doi: 10.1021/bm300835r. Epub 2012 Jul 13.
We report a facile approach to immobilize pH-cleavable polymer-drug conjugates in mussel-inspired polydopamine (PDA) capsules for intracellular drug delivery. Our design takes advantage of the facile PDA coating to form capsules, the chemical reactivity of PDA films, and the acid-labile groups in polymer side chains for sustained pH-induced drug release. The anticancer drug doxorubicin (Dox) was conjugated to thiolated poly(methacrylic acid) (PMA(SH)) with a pH-cleavable hydrazone bond, and then immobilized in PDA capsules via robust thiol-catechol reactions between the polymer-drug conjugate and capsule walls. The loaded Dox showed limited release at physiological pH but significant release (over 85%) at endosomal/lysosomal pH. Cell viability assays showed that Dox-loaded PDA capsules enhanced the efficacy of eradicating HeLa cancer cells compared with free drug under the same assay conditions. The reported method provides a new platform for the application of stimuli-responsive PDA capsules as drug delivery systems.
我们报告了一种简便的方法，将 pH 可裂解的聚合物-药物偶联物固定在贻贝类聚多巴胺 (PDA) 胶囊中，用于细胞内药物递送。我们的设计利用了简便的 PDA 涂层形成胶囊、PDA 薄膜的化学反应性以及聚合物侧链中的酸不稳定基团，以实现持续的 pH 诱导药物释放。抗癌药物阿霉素 (Dox) 通过 pH 可裂解的腙键与巯基化聚 (甲基丙烯酸) (PMA(SH)) 偶联，然后通过聚合物-药物偶联物与胶囊壁之间强大的巯基-儿茶酚反应固定在 PDA 胶囊中。负载的 Dox 在生理 pH 下释放有限，但在内涵体/溶酶体 pH 下释放显著（超过 85%）。细胞活力测定表明，与相同测定条件下的游离药物相比，载有 Dox 的 PDA 胶囊增强了根除 HeLa 癌细胞的功效。该报告的方法为刺激响应性 PDA 胶囊作为药物递送系统的应用提供了一个新的平台。
