Polymer--cisplatin conjugate nanoparticles for acid-responsive drug delivery.
Polymer--cisplatin conjugate nanoparticles for acid-responsive drug delivery.
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DOI：
10.1021/nn9014032
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发表时间：
2010-01-26
期刊：
影响因子：
17.1
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Aryal S;Hu CM;Zhang L
我们报道了由聚合物-顺铂结合物组成的尺寸小于100 nm的新型酸响应性治疗纳米粒(NPs)的合成。这些给药聚合物纳米粒的独特之处在于，每种顺铂药物都通过两个生物相容的两嵌段共聚物分子链的疏水链段共价偶联，从而在不同的环境酸度下产生了高度不同的药物释放曲线。我们证明，由于合成的聚合物-顺铂偶联物的临界胶束浓度(CMC)很低，因此很容易在水溶液中沉淀形成小于100 nm的纳米粒子。与游离顺铂相比，所得纳米粒具有良好的顺铂载药量、良好的酸响应性药物释放动力学和增强的体外细胞毒性。作为一种环境敏感的药物输送载体，这些纳米粒子可能会在pH值为中性的血液中减少药物循环中的药物损失，并在NPs被靶细胞内吞下后引发快速的细胞内药物释放。这一独特的药物释放谱有望通过在肿瘤细胞内快速释放大剂量化疗药物来抑制癌细胞的化疗耐药性，从而提高药物有效载荷的治疗效果。
We report the synthesis of novel acid-responsive therapeutic nanoparticles (NPs) with sub-100 nm size consisting of polymer-cisplatin conjugates. The uniqueness of these drug delivery polymeric NPs lies in the covalent conjugation of each cisplatin drug to the hydrophobic segment of two biocompatible diblock copolymer chains through hydrazone bond, resulting in highly differential drug release profile at different environmental acidity. We demonstrate that the synthesized polymer-cisplatin conjugates can readily precipitate to form sub-100 nm NPs in aqueous solution due to their very low critical micellar concentration (CMC). The resulting NPs show well controlled cisplatin loading yield, excellent acid-responsive drug release kinetics, and enhanced in vitro cytotoxicity against ovarian cancer cells as compared to free cisplatin. As an environmentally sensitive drug delivery vehicle, these NPs can potentially minimize the drug loss during NP circulation in the blood where the pH value is neutral and trigger rapid intracellular drug release after the NPs are endocytosed by the target cells. This characteristic drug release profile holds the promise to suppress cancer cell chemoresistance by rapidly releasing a high dose of chemotherapy drugs inside the tumor cells, thereby improving the therapeutic efficacy of the drug payload.
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