期刊
CARBOHYDRATE POLYMERS
卷 229, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2019.115498
关键词
Amphiphilic chitosan derivate; Micelles; Prostate tumor targeting; pH-responsive release; Paclitaxel
资金
- National Natural Science Foundation of China [81930099 81773664, 81873017, 81503003]
- National Basic Research Program of China [2015CB755504]
- 111 Project from the Ministry of Education of China
- State Administration of Foreign Expert Affairs of China [111-2-07, B17047]
- Open Project of State Key Laboratory of Natural Medicines [SKLNMZZCX201811]
- Double First-Class University project [CPU2018GY47, CPU2018GF10]
- Key Medical Youth Talent Project of Jiangsu Province [QNRC2016631]
Controlled release and tumor-selective distribution are highly desirable for anticancer nanomedicines. Here, we design and synthesize an anisamide-conjugated N-octyl-N,O-maleoyl-O-phosphoryl chitosan (a-OMPC) which can form amphiphilic micelles featuring pH-responsive release and high affinity to sigma-1 receptor-overexpressed tumors for paclitaxel (PTX) delivery. Thereinto, maleoyl and phosphoryl groups cooperatively contribute to pH-responsive drug release due to a conversion from hydrophile to hydrophobe in the acidic microenvironment of endo/lysosomes. We demonstrated that PTX-loaded a-OMPC micelles (PTX-aM) enhanced the cellular internalization via the affinity between anisamide and sigma-1 receptor, rapidly released drug in endo/lysosomes and elevated the cytotoxicity against PC-3 cells. The in vivo studies further verified that PTX-aM could largely accumulate at the tumor site even after 24 h of administration, resulting in obvious inhibition effect and prolonged survival period in PC-3 tumor xenograft-bearing mice. Moreover, OMPC showed no obvious hemolytic and acute toxicity. Collectively, this chitosan derivate holds a promising potential in application of prostate cancer-targeted drug delivery system.
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