Two-step synthesis of multivalent cancer-targeting constructs

Jill M. Stukel, Ronald C. Li, Heather D. Maynard, Michael Caplan

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Selective targeting of constructs to pathological cells by conjugating one or more ligands for an overexpressed receptor has been proposed to enhance the delivery of therapeutics to and imaging of specific cells of interest. Previous work in our lab has demonstrated the efficacy of targeting glioblastoma cells with a multivalent, biomacromolecular construct targeted to the α6β1-integrin. However, solid-phase synthesis of this construct was inefficient in terms of cost and number of steps. Here we show proof-of-concept of a two-step synthesis that can be used to create similar constructs targeted to glioblastoma cells. Specifically, a well-defined aldehyde side chain polymer was synthesized and oxime chemistry was employed to conjugate ligands specific for the α6β1- integrin. These constructs were then tested in competitive binding, fluorescence binding, and toxicity assays, through which we demonstrate that constructs are multivalent, preferentially target glioblastoma cells, and are nontoxic. Rapid, potentially low-cost synthesis of targeting constructs will enable their use in the clinic and for personalized medicine.

Original languageEnglish (US)
Pages (from-to)160-167
Number of pages8
JournalBiomacromolecules
Volume11
Issue number1
DOIs
StatePublished - Jan 11 2010

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Integrins
Ligands
Oximes
Aldehydes
Medicine
Toxicity
Costs
Assays
Polymers
Fluorescence
Imaging techniques

ASJC Scopus subject areas

  • Bioengineering
  • Materials Chemistry
  • Polymers and Plastics
  • Biomaterials

Cite this

Stukel, J. M., Li, R. C., Maynard, H. D., & Caplan, M. (2010). Two-step synthesis of multivalent cancer-targeting constructs. Biomacromolecules, 11(1), 160-167. https://doi.org/10.1021/bm9010276

Two-step synthesis of multivalent cancer-targeting constructs. / Stukel, Jill M.; Li, Ronald C.; Maynard, Heather D.; Caplan, Michael.

In: Biomacromolecules, Vol. 11, No. 1, 11.01.2010, p. 160-167.

Research output: Contribution to journalArticle

Stukel, JM, Li, RC, Maynard, HD & Caplan, M 2010, 'Two-step synthesis of multivalent cancer-targeting constructs', Biomacromolecules, vol. 11, no. 1, pp. 160-167. https://doi.org/10.1021/bm9010276
Stukel, Jill M. ; Li, Ronald C. ; Maynard, Heather D. ; Caplan, Michael. / Two-step synthesis of multivalent cancer-targeting constructs. In: Biomacromolecules. 2010 ; Vol. 11, No. 1. pp. 160-167.
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