期刊
PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
卷 31, 期 3, 页码 347-356出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/ppsc.201300120
关键词
ASGPR-mediated cellular uptake; biodistribution; galactose; gold nanoparticles; short polyethylene glycol
资金
- National 973 Basic Research Program [2012CB933800]
- Natural Science Foundation of China [30900337]
- Program for New Century Excellent Talents in University [NCET-10-0816]
- 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
- Open Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [SKLNMKF201307]
For the specific liver parenchymal cell delivery, a series of short heterobifunctional poly(ethylene glycol) (PEG) derivatives containing dimercapto and galactose (Gal) terminals is synthesized for the preparation of gold conjugates. The Gal density on the surface of all gold conjugates can be well controlled and the prepared gold conjugates are stable in various media, even in the presence of serum. For the liver targeting and reflectance imaging applications, the structure-function relationships of this platform, including the influence of the PEG molecular weight and the Gal ligand coverage of hybrid particles on the cytotoxicity and cellular recognition of tumor cells in vitro and on their liver-targeting ability in small animals, are studied. Biocompatibility results show that HepG2 cells are more sensitive than HeLa cells to gold conjugates. Cellular uptake studies demonstrate that a lower PEG molecular weight, a higher Gal density, or a higher gold concentration can increase the cellular uptake efficiency of these hybrid particles in HepG2 cells when the other parameters are constant. The results reveal the importance of parameter modulation for the design and control of nanoprobes and the gold conjugates with short PEG chains and a high Gal density are a potential vector for active-targeting therapy.
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