State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR, China.
Int J Pharm. 2020 Nov 15;589:119870. doi: 10.1016/j.ijpharm.2020.119870. Epub 2020 Sep 10.
The efficient delivery of chemotherapeutic drugs to the tumor tissues unavoidably encounters numerous obstacles, such as poor tumor targeting capability, slow intracellular drug release and massive accumulation in the liver. In this study, by self-assembling methoxy poly (ethylene glycol)-poly (lactide) block copolymer (mPEG-PLA) and hyaluronic acid-paclitaxel conjugate (HA-PTX), the composite nanoparticles (mPPHP NPs) were fabricated for efficient therapy of cancer. mPPHP NPs formed self-assembled nanoparticles (116 nm in diameter) with a narrow size distribution; and showed a rapid release of PTX in the presence of hyaluronidase and esterase. mPPHP NPs exhibited enhanced internalization by cells via CD44 receptors and selected cytotoxicity against A549 cells in vitro. More importantly, compared with other PTX formulations, mPPHP NPs were demonstrated to present the reduced liver accumulation, excellent tumor-targeting ability and superior antitumor efficacy in vivo, with a TIR of 75.9%. The multifunctional composite nanoparticles could be developed as a promising nano-carrier for improved therapeutic efficacy.
化疗药物向肿瘤组织的有效递送不可避免地会遇到许多障碍，例如肿瘤靶向能力差、细胞内药物释放缓慢以及在肝脏中大量积累。在这项研究中，通过自组装甲氧基聚（乙二醇）-聚（乳酸）嵌段共聚物（mPEG-PLA）和透明质酸-紫杉醇缀合物（HA-PTX），制备了用于癌症有效治疗的复合纳米颗粒（mPPHP NPs）。mPPHP NPs 形成了自组装纳米颗粒（直径为 116nm），具有较窄的粒径分布；并且在透明质酸酶和酯酶存在下，PTX 快速释放。mPPHP NPs 通过细胞表面的 CD44 受体增强了细胞内化作用，并在体外对 A549 细胞表现出选择毒性。更重要的是，与其他 PTX 制剂相比，mPPHP NPs 在体内表现出较低的肝脏蓄积、优异的肿瘤靶向能力和卓越的抗肿瘤疗效，TIR 为 75.9%。这种多功能复合纳米颗粒可以开发为一种有前途的纳米载体，以提高治疗效果。
