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Hyperpolarized Xenon for NMR and MRI Applications
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Cryptophane-folate biosensor for (129)xe NMR.

Najat S Khan1, Brittany A Riggle, Garry K Seward

  • 1Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104, United States.

Bioconjugate Chemistry
|December 2, 2014
PubMed
Summary

A novel folate-conjugated cryptophane biosensor targets cancer cells by binding to folate receptors. This targeted cancer therapy approach shows high cellular uptake in cancer cells and is non-toxic.

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Area of Science:

  • Bioconjugation Chemistry
  • Molecular Imaging
  • Cancer Biology

Background:

  • Membrane-bound folate receptors are overexpressed in various human cancers, making them attractive targets for cancer therapy.
  • Developing targeted delivery systems is crucial for enhancing drug efficacy and reducing side effects in cancer treatment.

Purpose of the Study:

  • To develop and characterize a novel folate-conjugated cryptophane biosensor for targeted delivery to cancer cells via folate receptors.
  • To evaluate the biosensor's cellular uptake, targeting specificity, and toxicity in cancer and normal cell lines.

Main Methods:

  • Synthesis of folate-conjugated cryptophane incorporating a Cy3 fluorophore and solubilizing peptide through a 20-step nonlinear process.
  • Hyperpolarized (129)Xe NMR to confirm xenon binding.
  • Confocal laser scanning microscopy and flow cytometry for cellular internalization studies.
  • Competitive blocking assays to confirm folate receptor-mediated endocytosis.
  • MTT assay to assess cytotoxicity.

Main Results:

  • Successful synthesis of the folate-conjugated cryptophane biosensor.
  • Confirmation of xenon binding to the biosensor using (129)Xe NMR.
  • Demonstration of folate receptor-mediated endocytosis and targeted cellular internalization.
  • 10-fold higher uptake in KB cancer cells (overexpressing folate receptors) compared to HT-1080 cells (normal folate receptor expression).
  • The biosensor exhibited no toxicity in tested cell lines at relevant concentrations.

Conclusions:

  • The developed folate-conjugated cryptophane biosensor effectively targets cancer cells overexpressing folate receptors.
  • The biosensor demonstrates specific cellular uptake and is non-toxic, indicating its potential as a targeted imaging or therapeutic agent for cancer.