期刊
BIOMATERIALS
卷 30, 期 10, 页码 1928-1936出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2008.12.038
关键词
Gold nanoparticle; Polyethylene glycol; Thioctic acid; Biodistribution; Pharmacokinetics
资金
- National Cancer Institute [R01 CA119387]
- John S. Dunn Foundation
- NATIONAL CANCER INSTITUTE [U24CA126577, R01CA119387] Funding Source: NIH RePORTER
Polyethylene glycol (PEG)-coated (pegylated) gold nanoparticles (AuNPs) have been proposed as drug carriers and diagnostic contrast agents. However, the impact of particle characteristics on the biodistribution and pharmacokinetics of pegylated AuNPs is not clear. We investigated the effects of PEG molecular weight, type of anchoring ligand, and particle size on the assembly properties and colloidal stability of PEG-coated AuNPs. The pharmacokinetics and biodistribution of the most stable PEG-coated AuNPs in nude mice bearing subcutaneous A431 squamous tumors were further studied using (111)Inlabeled AuNPs. AuNPs coated with thioctic acid (TA)-anchored PEG exhibited higher colloidal stability in phosphate-buffered saline in the presence of dithiothreitol than did AuNPs coated with monothiolanchored PEG. AuNPs coated with high-molecular-weight (5000 Da) PEG were more stable than AuNPs coated with low-molecular-weight (2000 Da) PEG. Of the 20-nm, 40-nm, and 80-nm AuNPs coated with TA-terminated PEC5000, the 20-nm AuNPs exhibited the lowest uptake by reticuloendothelial cells and the slowest clearance from the body. Moreover, the 20-nm AuNPs coated with TA-terminated PEC5000 showed significantly higher tumor uptake and extravasation from the tumor blood vessels than did the 40- and 80-nm AuNPs. Thus, 20-nm AuNPs coated with TA-terminated PEG(5000) are promising potential drug delivery vehicles and diagnostic imaging agents. (C) 2008 Elsevier Ltd. All rights reserved.
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