期刊
BIOMATERIALS
卷 32, 期 17, 页码 4118-4129出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.11.068
关键词
Nanoparticle; Dendrimers; Drug delivery; Flow cytometry; Hepatocyte
资金
- US National Science Foundation
- Coulter Foundation
- Department of Education
- Directorate For Engineering [747762] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys [747762] Funding Source: National Science Foundation
There is an urgent need for novel polymeric carriers that can selectively deliver a large dose of chemotherapeutic agents into hepatic cancer cells to achieve high therapeutic activity with minimal systemic side effects. PAMAM dendrimers are characterized by a unique branching architecture and a large number of chemical surface groups suitable for coupling of chemotherapeutic agents. In this article, we report the coupling of N-acetylgalactosamine (NAcGal) to generation 5 (G5) of poly(amidoamine) (PAMAM-NH(2)) dendrimers via peptide and thiourea linkages to prepare NAcGal-targeted carriers used for targeted delivery of chemotherapeutic agents into hepatic cancer cells. We describe the uptake of NAcGal-targeted and non-targeted G5 dendrimers into hepatic cancer cells (HepG2) as a function of G5 concentration and incubation time. We examine the contribution of the asialoglycoprotein receptor (ASGPR) to the internalization of NAcGal-targeted dendrimers into hepatic cancer cells through a competitive inhibition assay. Our results show that uptake of NAcGal-targeted G5 dendrimers into hepatic cancer cells occurs via ASGPR-mediated endocytosis. Internalization of these targeted carriers increased with the increase in G5 concentration and incubation time following Michaelis-Menten kinetics characteristic of receptor-mediated endocytosis. These results collectively indicate that G5-NAcGal conjugates function as targeted carriers for selective delivery of chemotherapeutic agents into hepatic cancer cells. (C) 2011 Elsevier Ltd. All rights reserved.
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