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Chemotherapeutic Drugs Interfere with Gene Delivery Mediated by Chitosan-Graft-Poly(ethylenimine)

Wing-Fu Lai1, Marie C Lin2

  • 1School of Medicine, Shenzhen University, Shenzhen, China; Department of Mechanical Engineering, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Plos One
|May 12, 2015
PubMed

Insights

Chemotherapy drugs can impact gene therapy effectiveness. This study found that cis-diamminedichloroplatinum(II) and teniposide significantly reduced gene transfer, while temozolomide did not, highlighting drug-specific effects in combined chemo-gene therapy.

Area of Science:

  • Biomedical Engineering
  • Molecular Therapy
  • Drug Delivery Systems

Background:

  • Combined chemo-gene therapy offers therapeutic potential but its efficiency can be affected by drug interactions.
  • Limited data exists on how chemotherapeutic agents influence gene transfer processes.
  • Chitosan-graft-poly(ethylenimine) is a promising non-viral vector for gene delivery.

Purpose of the Study:

  • To investigate the interference of specific chemotherapeutic drugs with polyplex formation and gene transfection.
  • To evaluate the impact of drug mechanism of action on gene transfer efficiency.
  • To determine how different gene/drug co-formulations affect transfection outcomes.

Main Methods:

  • Utilized chitosan-graft-poly(ethylenimine) as a gene delivery vector.
  • Examined the effects of teniposide, cis-diamminedichloroplatinum(II), and temozolomide on polyplex formation.
  • Assessed the influence of these drugs on transgene expression following co-delivery with plasmid DNA.

Main Results:

  • Drug interference with gene transfer varied based on the chemotherapeutic agent's mechanism of action.
  • Transgene expression was significantly suppressed by cis-diamminedichloroplatinum(II) and teniposide.
  • Temozolomide did not show significant suppression of transgene expression.
  • Interference with transfection efficacy was dependent on specific gene/drug co-formulations.

Conclusions:

  • Certain chemotherapeutic drugs can negatively impact the efficiency of gene therapy.
  • The choice of chemotherapeutic agent is critical when considering combined chemo-gene therapy strategies.
  • Further research is needed to optimize combined chemo-gene therapy protocols to mitigate drug-induced interference.

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