期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 103, 期 5, 页码 1487-1496出版社
WILEY
DOI: 10.1002/jps.23928
关键词
nanoparticles; paclitaxel; D-Glucosamine; GLUT; tumor-targeting delivery system; biomaterials; drug delivery system; biodegradable; polymers; cancer chemotherapy
资金
- National Key Basic Research Program of China [2013CB932502]
- National Natural Science Foundation of China [81302716, 81302710]
- National Science and Technology Major Project [2012ZX09304004]
- Natural Science Foundation of Jiangsu Province [BK2012445]
- ordinary university natural science research project of Jiangsu Province [13KJB350004]
- Advanced Talent Foundation of Jiangsu University [13JDG013]
- School of Pharmacy, Fudan University
- Open Project Program of Key Lab of Smart Drug Delivery (Fudan University)
- Ministry of Education, China [SDD2012-4]
The poor selectivity of chemotherapeutics for cancer treatment may lead to dose-limiting side effects that compromise clinical outcomes. To solve the problem, surface-functionalized polymer nanoparticles are regarded as promising tumor-targeting delivery system. On the basis of glucose transporter (GLUT) overexpression on cancer cells, D-glucosamine-conjugated and paclitaxel-loaded poly(ethylene glycol)-co-poly(trimethylene carbonate) copolymer nanoparticles (DGlu-NP/PTX) were developed as potential tumor-targeting drug delivery system in this study. Because of the high affinity between D-glucosamine and GLUT, DGlu-NP/PTX could target to tumor tissue through GLUT-mediated endocytosis to improve the selectivity of PTX. DGlu-NP/PTX was prepared by emulsion/solvent evaporation technique and characterized in terms of morphology, size, and zeta potential. In vitro evaluation of two-dimensional cells and three-dimensional tumor spheroids revealed that DGlu-NP/PTX was more potent than those of plain nanoparticles (NP/PTX) and Taxol. In vivo multispectral fluorescent imaging indicated that DGlu-NP had higher specificity and efficiency on subcutaneous xenografts tumor of mouse. Furthermore, DGlu-NP/PTX showed the greatest tumor growth inhibitory effect on in vivo subcutaneous xenografts model with no evident toxicity. Therefore, these results demonstrated that DGlu-NP/PTX could be used as potential vehicle for cancer treatment. (C) 2014 Wiley Periodicals, Inc.
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