Effect of Hydrophobic Chain Length in Amphiphilic Chitosan Conjugates on Intracellular Drug Delivery and Smart Drug Release of Redox-Responsive Micelle

被引:4
|
作者
Yuan, Yuting [1 ,2 ,3 ]
Tan, Wenqiang [1 ,3 ]
Mi, Yingqi [1 ,3 ]
Wang, Linqing [1 ,2 ,3 ]
Qi, Zhen [4 ]
Guo, Zhanyong [1 ,2 ,3 ]
机构
[1] Chinese Acad Sci, Yantai Inst Coastal Zone Res, Key Lab Coastal Biol & Bioresource Utilizat, Yantai 264003, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[3] Chinese Acad Sci, Ctr Ocean Mega Sci, Qingdao 266071, Peoples R China
[4] Yantai Univ, Coll Life Sci, Yantai 264005, Peoples R China
关键词
different hydrophobic chain length; low molecular weight chitosan; trigger-release; POLYMERIC MICELLES; BLOCK-COPOLYMERS; ANTICANCER DRUG; SENSITIVE MICELLES; MIXED MICELLES; CO-DELIVERY; CANCER; DOCETAXEL;
D O I
10.3390/md22010018
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Three redox-sensitive nanocarriers were rationally designed based on amphiphilic low molecular weight chitosan-cystamine-octylamine/dodecylamin/cetylamine (LC-Cys-OA, LC-Cys-DA, LC-Cys-CA) conjugates containing disulfide linkage for maximizing therapeutic effect by regulating hydrophobic interaction. The resultant spherical micelles had the characteristics of low CMC, suitable size, excellent biosafety and desired stability. The drug-loaded micelles were fabricated by embedding doxorubicin (Dox) into the hydrophobic cores. The effect of hydrophobic chain lengths of amphiphilic conjugates on encapsulation capacity, redox sensitivity, trigger-release behavior, cellular uptake efficacy, antitumor effect and antimigratory activity of Dox-loaded micelles was systematically investigated. Studies found that Dox-loaded LC-Cys-CA micelle had superior loading capacity and enhanced redox sensitivity compared with the other two micelles. Release assay indicated that the three Dox-loaded micelles maintained sufficiently stability in normal blood circulation but rapidly disintegrated in tumor cells. More importantly, the LC-Cys-CA micelle with a longer hydrophobic chain length exhibited a higher accumulative Dox release percentage than the other two micelles. Additionally, an increase in hydrophobic chain lengths of amphiphilic conjugates improved cellular uptake efficiency, antitumor effect and antimigration activity of Dox-loaded micelles, which could be explained by enhanced loading ability and redox sensitivity. Our research was expected to provide a viable platform for achieving a desired therapeutic efficacy via the alteration of hydrophobic interaction.
引用
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页数:18
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