Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Mater Sci Eng C Mater Biol Appl. 2018 Jan 1;82:60-68. doi: 10.1016/j.msec.2017.08.063. Epub 2017 Aug 17.
Endosomal pH-responsive micellar nanoparticles were prepared by self-assembly of an amphiphilic poly(ethylene glycol)-acetal-paclitaxel (PEG-acetal-PTX) prodrug, and free PTX could be encapsulated in the hydrophobic core of the nanoparticles. These nanoparticles exhibited excellent storage stability for over 6months under normal conditions, but disassembled quickly in response to faintly acidic environment. Incorporating physical encapsulation and chemical conjugation, the PTX concentration in the nanoparticles solution could reach as high as 3665μg/mL, accompanying with a high drug loading capacity of 60.3%. Additionally, benefitting from the difference in drug release mechanism and rate between encapsulated PTX and conjugated PTX, a programmed drug release behavior was observed, which may result in higher intracellular drug concentration and longer action time. CCK-8 assays showed that the nanoparticles demonstrated superior antitumor activity than free PTX against both HeLa and MDA-MB-231 cells. These prodrug-based nanomedicines have a great potential in developing translational PTX formulations for cancer therapy.
通过自组装两亲性聚乙二醇缩醛紫杉醇（PEG-acetal-PTX）前药，制备了内体 pH 响应胶束纳米粒，游离 PTX 可以包裹在纳米粒的疏水核内。这些纳米粒在正常条件下具有超过 6 个月的优异储存稳定性，但在弱酸性环境下迅速解体。通过物理包封和化学结合，纳米粒溶液中的 PTX 浓度可高达 3665μg/mL，同时具有高达 60.3%的高载药量。此外，得益于包封 PTX 和结合 PTX 的药物释放机制和速率的差异，观察到了程序式药物释放行为，这可能导致细胞内药物浓度更高和作用时间更长。CCK-8 检测表明，与游离 PTX 相比，纳米粒对 HeLa 和 MDA-MB-231 细胞均表现出优异的抗肿瘤活性。这些基于前药的纳米药物在开发用于癌症治疗的转化型 PTX 制剂方面具有很大的潜力。
