Acid-Activatable Theranostic Unimolecular Micelles Composed of Amphiphilic Star-like Polymeric Prodrug with High Drug Loading for Enhanced Cancer Therapy,Molecular Pharmaceutics

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Acid-Activatable Theranostic Unimolecular Micelles Composed of Amphiphilic Star-like Polymeric Prodrug with High Drug Loading for Enhanced Cancer Therapy
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-10-16 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00704
Xiaoxiao Shi _{1,

2} , Meili Hou _{1,

2} , Shuang Bai _{1,

2} , Xiaoqian Ma _{1,

2} , Yong-E Gao _{1,

2} , Bo Xiao _{1,

3} , Peng Xue _{1,

2} , Yuejun Kang _{1,

2} , Zhigang Xu _{1,

2} , Chang Ming Li _{1,

2}

Affiliation

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.

中文翻译：

由两亲性星形聚合物前药与高载药量组成的可酸活化的治疗型单分子胶束，用于增强的癌症治疗

尽管在临床应用之前有一些主要的障碍需要克服，但是具有治疗学功能且副作用减少的刺激响应性纳米药物引起了越来越多的关注。在本文中，我们提出了一种基于两亲性星形聚合物前药的可酸活化的治疗性单分子胶束，以系统地解决典型的现有问题。该智能聚合物前药的优选大小为约35 nm，在水溶液中的胶束稳定性强，这有利于长期血液循环和从肿瘤血管的有效渗出。值得注意的是，聚合前药的载药率高达53.1 wt％，它对肿瘤细胞（HeLa细胞和MCF-7细胞）的诱导毒性要比正常细胞（HUVEC细胞）高得多，这表明它具有自发的肿瘤特异性靶向能力。此外，聚合物前药可作为荧光纳米探针，被肿瘤细胞中的酸性微环境激活，可用作肿瘤诊断的有前途的平台。在此卓越的抗肿瘤作用体外研究证明了该前药作为药物输送和癌症治疗的有前途平台的潜力。

更新日期：2017-10-16

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