期刊
BIOTECHNOLOGY AND BIOENGINEERING
卷 108, 期 12, 页码 2999-3008出版社
WILEY
DOI: 10.1002/bit.23255
关键词
tumor spheroids; PAMAM dendrimers; siRNA delivery; tumor drug penetration; RGD peptides
资金
- NIH [R01 EB008278-07]
- NSF [DGE-0504497]
The mechanisms governing the efficient tumor spheroid penetration and transport by poly(amidoamine) (PAMAM) dendrimers displaying varying numbers of cyclic RGD targeting peptides (2, 3, 7, or 10) were evaluated in this work. The cell-free binding affinities and cellular internalization kinetics of PAMAM-RGD conjugates to malignant glioma cells were determined experimentally, and the results were incorporated into a mathematical model to predict the transport of these materials through a multicellular tumor spheroid. The theoretical analysis demonstrated that greater RGD crosslinking may improve transport through tumor spheroids due to their decreased integrin-binding affinity. This study provides evidence that altering the density of tumor-targeting ligands from a drug delivery platform is a feasible way to optimize the tumor-penetration efficiency of an anticancer agent, and provides insight into the physicochemical mechanisms governing the relative effectiveness of these conjugates. Biotechnol. Bioeng. 2011; 108: 2999-3008. (C) 2011 Wiley Periodicals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据