Department of Mastopathy, The Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of TCM), Nanjing, China.
The Department of Oncology, The Affiliated Shuyang Hospital of Xuzhou Medical University, Suqian, China.
Drug Deliv. 2020 Dec;27(1):825-835. doi: 10.1080/10717544.2020.1770373.
Multidrug resistance (MDR) of cancer cells is a significant challenge in chemotherapy, highlighting the urgent medical need for simple and reproducible strategies to reverse this process. Here, we report the development of an active tumor-targeting and redox-responsive nanoplatform (PA-ss-NP) using hyaluronic acid--cystamine dihydrochloride-poly-ε-(benzyloxycarbonyl)-L-lysine (HA-ss-PLLZ) to co-deliver paclitaxel (PTX) and apatinib (APA) for effective reversal of MDR. This smart nanoplatform specifically bound to CD44 receptors, leading to selective accumulation at the tumor site and uptake by MCF-7/ADR cells. Under high concentrations of cellular glutathione (GSH), the nanocarrier was degraded rapidly with complete release of its encapsulated drugs. Released APA effectively inhibited the function of the P-glycoprotein (P-gp) drug pump and improved the sensitivity of MDR cells to chemotherapeutic agents, leading to the recovery of PTX chemosensitivity in MDR cells. As expected, this newly developed intelligent drug delivery system could effectively control MDR, both and .
癌细胞的多药耐药性（MDR）是化疗的一个重大挑战，突显了迫切需要简单且可重复的策略来逆转这一过程。在这里，我们报告了一种使用透明质酸-胱胺二盐酸盐-聚-ε-（苄氧羰基）-L-赖氨酸（HA-ss-PLLZ）制备主动肿瘤靶向和氧化还原响应纳米平台（PA-ss-NP）的方法，用于共递送紫杉醇（PTX）和阿帕替尼（APA），以有效逆转 MDR。这种智能纳米平台特异性结合 CD44 受体，导致其在肿瘤部位的选择性积累和 MCF-7/ADR 细胞的摄取。在高浓度的细胞谷胱甘肽（GSH）下，纳米载体迅速降解，其包裹的药物完全释放。释放的 APA 有效抑制了 P-糖蛋白（P-gp）药物泵的功能，提高了 MDR 细胞对化疗药物的敏感性，使 MDR 细胞对 PTX 的化疗敏感性恢复。正如预期的那样，这种新开发的智能药物递送系统能够有效地控制 MDR，无论是体内还是体外。
