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An Aptamer That Rapidly Internalizes into Cancer Cells Utilizes the Transferrin Receptor Pathway.

Xirui Song1,2, Haixiang Yu1, Cynthia Sullenger3

  • 1Department of Surgery, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA.

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|May 16, 2023
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Summary

This study reveals that the E3 aptamer targets cancer cells by binding to transferrin receptor 1 (TfR1). This aptamer-drug conjugate shows promise for targeted cancer therapy by delivering cytotoxic drugs specifically to tumor cells.

Keywords:
aptamercancercanine cancerdrug targetingtransferrin receptor

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Targeted cancer therapy aims to deliver drugs specifically to cancer cells.
  • Aptamers offer advantages for drug targeting due to their specificity, size, and manufacturability.
  • Previous research identified the E3 aptamer for targeting and delivering drugs to human cancer cells.

Purpose of the Study:

  • To elucidate the molecular mechanism by which the E3 aptamer targets cancer cells.
  • To investigate the role of transferrin receptor 1 (TfR1) in E3 aptamer internalization.
  • To develop a molecular model of E3 aptamer binding to TfR1.

Main Methods:

  • Investigated E3 aptamer binding affinity and competition with transferrin (Tf) for TfR1.
  • Utilized gene knockdown and knockin of human TfR1 to assess its effect on E3 binding.
  • Developed a molecular model of the E3 aptamer-TfR1 interaction.

Main Results:

  • The E3 aptamer selectively internalizes into cancer cells via the transferrin receptor 1 (TfR1) pathway.
  • E3 exhibits high-affinity binding to recombinant human TfR1 and competes with Tf.
  • Modulation of TfR1 expression levels directly impacts E3 aptamer cell binding.

Conclusions:

  • The E3 aptamer utilizes TfR1 for selective internalization into cancer cells.
  • This mechanism supports the development of E3 aptamer-based targeted cancer therapeutics.
  • The findings provide a molecular basis for E3 aptamer-TfR1 interactions in drug delivery.