4.6 Article

Binding and Transport of PAMAM-RGD in a Tumor Spheroid Model: The Effect of RGD Targeting Ligand Density

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

  1. NIH [R01 EB008278-07]
  2. NSF [DGE-0504497]

向作者/读者索取更多资源

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.

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