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Biotechnol Bioeng. 2011 Dec;108(12):2999-3008. doi: 10.1002/bit.23255. Epub 2011 Jul 19.

Binding and transport of PAMAM-RGD in a tumor spheroid model: the effect of RGD targeting ligand density.

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1
Department of Chemical and Biochemical Engineering, Rutgers University, 599 Taylor Rd, Piscataway, New Jersey 08854, USA.

Abstract

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.

PMID:
21755497
PMCID:
PMC3193538
DOI:
10.1002/bit.23255
[Indexed for MEDLINE]
Free PMC Article
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