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Updated: Feb 8, 2026

An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
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An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses

Published on: November 28, 2010

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Correlating quantitative tumor accumulation and gene knockdown using SPECT/CT and bioluminescence imaging within an

Steven K Jones1, Kirk Douglas2, Anthony F Shields2

  • 1Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA.

Biomaterials
|June 24, 2018
PubMed

Insights

Targeted nanoparticles effectively delivered siRNA to ovarian tumors and metastases, achieving significant gene knockdown. Intraperitoneal injection showed promising tumor accumulation and gene silencing, highlighting potential for ovarian cancer therapy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Ovarian cancer presents significant treatment challenges.
  • Effective delivery of small interfering RNA (siRNA) is crucial for gene silencing therapies.
  • Targeted nanoparticle delivery systems can improve therapeutic efficacy.

Purpose of the Study:

  • To evaluate the efficacy of novel tri-block copolymer nanoparticles for siRNA delivery in an orthotopic ovarian cancer model.
  • To compare targeted (folic acid ligand) versus non-targeted nanoparticles.
  • To correlate nanoparticle tumor accumulation with in vivo gene silencing.

Main Methods:

  • Development of hyperbranched polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) (hyPEI-g-PCL-b-PEG) nanoparticles, with and without folic acid.
  • Utilized an orthotopic SKOV-3/LUC FRα-overexpressing ovarian cancer model in mice.
  • Assessed siRNA delivery and tumor accumulation using gamma scintillation counting and confocal microscopy.
  • Quantified gene silencing via firefly luciferase expression knockdown.

Main Results:

  • Both targeted and non-targeted nanoparticles effectively delivered siRNA to primary tumors and metastases.
  • Intraperitoneal (I.P.) administration resulted in significant tumor uptake (6% ID/g) and a 62% knockdown of luciferase expression.
  • Intravenous (I.V.) administration showed a slight advantage for targeted nanoparticles in tumor accumulation, but both had high liver uptake.
  • Nanoparticle stability was confirmed via serum albumin binding studies.

Conclusions:

  • PEI-g-PCL-b-PEG-Fol conjugates demonstrate potential as a promising platform for ovarian cancer gene knockdown therapy.
  • Intraperitoneal delivery of these targeted nanoparticles is effective for achieving significant gene silencing in both primary and metastatic ovarian tumors.
  • Further research is warranted to optimize delivery and minimize off-target effects like liver accumulation.
Keywords:
Folate receptor alphaFolate receptor targetingOvarian cancerOvarian cancer xenograftPolymer micelleplexessiRNA delivery

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