Glioblastoma targeting via integrins is concentration dependent

Elena V. Rosca, Robert J. Gillies, Michael Caplan

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

A novel approach to treat cancer more selectively is achieved by targeting drugs to cells via conjugating the drug or imaging agent to an antibody or ligand for a cell surface receptor that is over-expressed by the target cell population. Previous work by us has suggested that enhanced specificity can be obtained by multivalency of binding moieties. In this study we investigated the binding specificity of a multivalent construct including three peptides segments (TWYKIAFQRNRK), which bind the a6b1-integrin, linked by poly(ethylene glycol) spacers. The binding specificity of the constructs was calculated by quantifying their binding to target cells (glioma cells, SF 767) relative to non-targeted cells (normal human astrocytes, NHA). Dodecapeptide constructs (monovalent) exhibit specificity equal to the ratio of receptor expression at all concentrations. However, trivalent constructs demonstrated a sharp increase in specificity at concentrations less than the affinity of the receptor-ligand bond (4.28 μM). These experiments (conducted at 4°C) were consistent with the theoretical prediction and indicate that the biophysical model captures the basic trend of the data in the absence of receptor internalization, although the concentration at which increased specificity is observed is greater than predicted. The biophysical model does not predict the results of 37°C experiments, and this is shown to be due to internalization which occurs at 37°C but not at 4°C.

Original languageEnglish (US)
Pages (from-to)408-417
Number of pages10
JournalBiotechnology and Bioengineering
Volume104
Issue number2
DOIs
StatePublished - Oct 1 2009

Fingerprint

Glioblastoma
Integrins
Ligands
Cell Surface Receptors
Antibodies
Peptides
Polyethylene glycols
Experiments
Cells
Imaging techniques
Pharmaceutical Preparations
Ethylene Glycol
Health Services Needs and Demand
Drug Delivery Systems
Glioma
Astrocytes
Neoplasms

Keywords

  • Cell surface receptor
  • Drug delivery
  • Glioblastoma
  • Macromolecular substance
  • Protein-binding

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Glioblastoma targeting via integrins is concentration dependent. / Rosca, Elena V.; Gillies, Robert J.; Caplan, Michael.

In: Biotechnology and Bioengineering, Vol. 104, No. 2, 01.10.2009, p. 408-417.

Research output: Contribution to journalArticle

Rosca, Elena V. ; Gillies, Robert J. ; Caplan, Michael. / Glioblastoma targeting via integrins is concentration dependent. In: Biotechnology and Bioengineering. 2009 ; Vol. 104, No. 2. pp. 408-417.
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