Conjugated Polymer Nanoparticles for Targeted Anticancer Chemodynamic Therapy

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The UCF invention delivers iron to targeted tumor cells to enable ferroptosis-assisted chemodynamic therapy. Image reprinted with permission from Molecular Pharmaceutics 2019, 16, 4852−4866, DOI: 10.1021/acs.molpharmaceut.9b00737. American Chemical Society.
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Researchers
Khalaf Jasim, Ph.D.
Andre Gesquiere, Ph.D.
External Link (sciences.ucf.edu)
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Brion Berman
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US Patent Pending
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Ultrastable and Biofunctionalizable Conjugated Polymer Nanoparticles With Encapsulated Iron for Ferroptosis Assisted Chemodynamic Therapy
Molecular Pharmaceutics, 2019 Nov. 4, doi:10.1021/acs.molpharmaceut.9b00737

Tumor-targeting nanoparticles induce ferroptosis in cancer cells without need for external activation

Researchers at the University of Central Florida have developed a tumor-targeting nanoparticle system for chemodynamic therapy (CDT). The conjugated polymer nanoparticles (CPNPs) deliver iron for CDT at the targeted tumor site. In contrast to photodynamic therapy, which requires external light activation, CDT does not depend on external activation. The system initiates tumor killing through ferroptosis, an iron-dependent and reactive oxygen species (ROS)-based form of cell death that is not heavily dependent on oxygen availability. This approach may be especially promising for the treatment of multidrug-resistant or photodynamic-resistant cancers such as hypoxic tumors.

Technical Details

Due to the synthesis process, the CPNPs are loaded with iron ions in their core. Additionally, the flexible nanoparticle design allows for surface modification with a target cancer ligand. The iron reacts with the endogenous hydrogen peroxide that is elevated in many types of tumors to form ROS, leading to cell damage and death. The reaction does not require external stimuli for ROS production.

The CPNPs have been tested against melanoma cancer cells. CPNPs conjugated with endothelin-3 ligand demonstrated direct targeting to melanoma cancer cells that overexpress endothelin-B receptors. The CPNPs induced dose-dependent tumor cell death in the targeted cells, more than 80 percent at the higher doses tested, and minimal cell death in non-targeted cells.

Stage of Development

The CPNPs have demonstrated anti-tumor activity against melanoma cancer cell lines.

Benefits

  • Mechanism is not dependent on external activation
  • Mechanism is not heavily dependent on oxygen availability
  • Flexible nanoparticle design enables conjugation with target cancer ligand

Applications

  • Tumor-targeting nanotherapy, may be especially beneficial for hypoxic tumors