期刊
BIOMATERIALS
卷 34, 期 38, 页码 10217-10227出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.09.008
关键词
Paclitaxel-conjugated gold nanoparticles; Double simultaneous stimulation; Target selection; Drug release; Tumor therapeutic efficacy; Overall performance improvement
资金
- Natural Science Foundation of China [30900337]
- Doctoral Fund of Ministry of Education of China [20090096120001]
- China Postdoctoral Science Foundation [2008440155, 201003566]
- Fundamental Research Funds for the Central Universities [JKQ2009026, JKP2011008]
- Qing Lan Project
- Program for New Century Excellent Talents in University [NCET-10-0816]
- Open Project Program of MOE Key Laboratory of Drug Quality Control and Pharmacovigilance [MKLDP2013MS04]
A series of thiol-terminated polyethylene glycol (PEG)-paclitaxel (PTX) derivatives are designed and synthesized to fabricate PTX-conjugated gold nanoparticles (PTX@GNPs) and improve their overall performance. By extending the molecular weight of PEG from 400 to 1000 Da, the optimized water solubility of the conjugate reaches 184 mg/mL, equal to 4.6 x 10(5) times that of PTX alone (0.4 mu g/mL). High drug loading is obtained by eliminating the steric hindrance between PTX molecules on the surface of GNPs. The gold conjugate shows double simultaneous stimulation-induced drug release behavior in the presence of both esterase and high concentrations of glutathione. The synergic release characteristics of this conjugate results in significant performance improvements, including prolonged circulation due to high stability in vivo, targeted release of PTX inside tumor cells, and increased tumor cell killing efficiency. Improving the in vitro properties of the conjugate not only significantly enhances its therapeutic efficacy in a murine liver cancer model, but also allows drug-conjugated gold nanoparticles to be used as a promising nanoprodrug system in the cancer therapeutics. (C) 2013 Elsevier Ltd. All rights reserved.
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