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Binding and transport of PAMAM-RGD in a tumor spheroid model: The effect of RGD targeting ligand density†
Article first published online: 19 JUL 2011
Copyright © 2011 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 108, Issue 12, pages 2999–3008, December 2011
How to Cite
Waite, C. L. and Roth, C. M. (2011), Binding and transport of PAMAM-RGD in a tumor spheroid model: The effect of RGD targeting ligand density. Biotechnol. Bioeng., 108: 2999–3008. doi: 10.1002/bit.23255
- Issue published online: 13 OCT 2011
- Article first published online: 19 JUL 2011
- Accepted manuscript online: 13 JUL 2011 08:49AM EST
- Manuscript Accepted: 20 JUN 2011
- Manuscript Revised: 26 MAY 2011
- Manuscript Received: 21 MAR 2011
- NIH. Grant Number: R01 EB008278-07
- NSF IGERT fellowship. Grant Number: DGE-0504497
- tumor spheroids;
- PAMAM dendrimers;
- siRNA delivery;
- tumor drug penetration;
- RGD peptides
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. © 2011 Wiley Periodicals, Inc.