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

Carolyn L. Waite, Charles M. Roth

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2999-3008
Number of pages10
JournalBiotechnology and Bioengineering
Volume108
Issue number12
DOIs
StatePublished - Dec 2011

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Keywords

  • PAMAM dendrimers
  • RGD peptides
  • SiRNA delivery
  • Tumor drug penetration
  • Tumor spheroids

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