Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University , Chongqing 400715, P. R. China.
Chongqing Engineering Research Centre for Micro-Nano Biomedical Materials and Devices , Chongqing 400715, P.R. China.
Mol Pharm. 2017 Nov 6;14(11):4032-4041. doi: 10.1021/acs.molpharmaceut.7b00704. Epub 2017 Oct 16.
Stimuli-responsive nanomedicine with theranostic functionalities with reduced side-effects has attracted growing attention, although there are some major obstacles to overcome before clinical applications. Herein, we present an acid-activatable theranostic unimolecular micelles based on amphiphilic star-like polymeric prodrug to systematically address typical existing issues. This smart polymeric prodrug has a preferable size of about 35 nm and strong micellar stability in aqueous solution, which is beneficial to long-term blood circulation and efficient extravasation from tumoral vessels. Remarkably, the polymeric prodrug has a high drug loading rate up to 53.1 wt%, which induces considerably higher cytotoxicity against tumor cells (HeLa cells and MCF-7 cells) than normal cells (HUVEC cells) suggesting a spontaneous tumor-specific targeting capability. Moreover, the polymeric prodrug can serve as a fluorescent nanoprobe activated by the acidic microenvironment in tumor cells, which can be used as a promising platform for tumor diagnosis. The superior antitumor effect in this in vitro study demonstrates the potential of this prodrug as a promising platform for drug delivery and cancer therapy.
具有治疗诊断功能的刺激响应型纳米医学可以减少副作用，尽管在临床应用之前还有一些重大障碍需要克服。在此，我们提出了一种基于两亲性星型聚合物前药的酸激活治疗诊断单分子胶束，以系统地解决典型的现有问题。这种智能聚合物前药的粒径约为 35nm，在水溶液中具有很强的胶束稳定性，有利于长期血液循环和从肿瘤血管中高效渗出。值得注意的是，聚合物前药具有高达 53.1wt%的高载药率，对肿瘤细胞（HeLa 细胞和 MCF-7 细胞）的细胞毒性明显高于正常细胞（HUVEC 细胞），表明其具有自发的肿瘤特异性靶向能力。此外，该聚合物前药可以作为一种荧光纳米探针，被肿瘤细胞中的酸性微环境激活，可作为肿瘤诊断的有前途的平台。该体外研究的优异抗肿瘤效果证明了该前药作为药物输送和癌症治疗的有前途的平台的潜力。
