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Folate receptor-targeted aminoglycoside-derived polymers for transgene expression in cancer cells

Sudhakar Godeshala1, Rajeshwar Nitiyanandan2, Brian Thompson1

  • 1Chemical Engineering Arizona State University Tempe AZ 85287.

Bioengineering & Translational Medicine
|January 10, 2018
PubMed

Insights

Novel folic acid-conjugated polymers effectively deliver therapeutic genes to cancer cells overexpressing folate receptors. These targeted nanoparticles show high efficacy and low toxicity, offering a promising approach for cancer therapy.

Area of Science:

  • Biotechnology
  • Nanomedicine
  • Oncology

Background:

  • Current chemotherapy faces limitations due to systemic toxicity and lack of specificity.
  • Folate receptors are overexpressed on various cancer cells, presenting a target for selective drug delivery.
  • Targeted delivery systems can enhance therapeutic efficacy while minimizing side effects.

Purpose of the Study:

  • To synthesize and characterize folic acid-conjugated aminoglycoside-derived polymers for targeted nucleic acid delivery.
  • To evaluate the efficacy and safety of these novel polymers in delivering transgenes to cancer cells.
  • To investigate the role of folate receptors in the cellular uptake and therapeutic effect of the targeted polymers.

Main Methods:

  • Synthesis and characterization of folic acid-conjugated aminoglycoside-derived polymers.
  • Evaluation of transgene expression in breast and bladder cancer cell lines.
  • Cytotoxicity assays to assess polymer safety.
  • Competitive inhibition studies using free folic acid to confirm receptor-mediated uptake.
  • Delivery of a TRAIL-expressing plasmid to induce cancer cell death.

Main Results:

  • Folic acid-conjugated polymers demonstrated significantly higher transgene expression compared to a standard transfection agent (Lipofectamine).
  • The developed polymers exhibited minimal cytotoxicity towards cancer cells.
  • Free folic acid significantly inhibited transgene expression, confirming folate receptor-mediated cellular uptake.
  • Delivery of the TRAIL gene using these polymers successfully induced apoptosis in cancer cells.

Conclusions:

  • Folic acid-conjugated aminoglycoside-derived polymers are effective and safe carriers for targeted nucleic acid delivery.
  • These polymers show promise for treating cancers that overexpress folate receptors.
  • The targeted delivery approach offers a potential strategy to improve anticancer therapeutic outcomes.
Keywords:
competitive inhibitionfolate receptorfolic acidgene deliveryneomycinparomomycintransgene expression

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