期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 3, 期 12, 页码 3364-3375出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.7b00618
关键词
CPT prodrug micelle; enhanced cellular uptake; reduction-triggered release; boronate ester; HepG2 cells
资金
- National Natural Science Foundation of China [51573050]
The aim of this research is to develop a novel type of camptothecin (CPT) prodrug micelles bearing boronate ester bonds as a smart nanosystem with enhanced cellular uptake and controlled drug release based on diblock copolymer abbreviated as PEG-BC-PG1u-ss-CPT. Particularly, boronate ester bond was introduced to achieve acid-triggered de-PEGylation and succeeding boronic acid-mediated enhanced cellular uptake. Besides, CPT was conjugated to the prodrug monomer through a disulfide bond to realize reduction-responsive drug release. The resultant copolymer PEG-BC-PG1u-ss-CPT could self-assemble into spherical nanomicelles in water. The degradation half-life time of PEG-BC-PGIu-ss-CPT copolymer decreased sharply from 96.27 h to only 5.7 h with pH value decreasing from 7.4 to 5.0, indicating the acid -degradable potential, which corresponded to size change monitoring. The cumulative CPT release from prodrug micelles increased significantly from 8.5 +/- 1.73 to 82.9 +/- 2.29% with an increase of dithiothreitol (DTT) concentration from 20 mu M to 10 mM at pH 7.4, illustrating the reduction responsive drug release property of prodrug micelles. The half maximal inhibitory concentration (IC50) value of prodrug micelles against HepG2 cells decreased from 1.06 to 0.68 pg/mL with the decrement of pH value from 7.4 to 6.0, proving that the utilization of boronate ester bonds was beneficial for enhancing antiproliferative activity. Interestingly, prodrug micelles exhibited enhanced cellular uptake ability against HepG2 cells compared to that of HL7702 cells, further confirming boronic acid -mediated enhanced endocytosis. In brief, this novel type of intelligent prodrug micelles possessed great potential as a smart nanosystem for antitumor drug delivery.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据