Targeting therapy-resistant cancer with iron nanoparticle-induced ferroptotic cell death

Lead Research Organisation: Swansea University
Department Name: Institute of Life Science Medical School

Abstract

Carboplatin has been the standard chemotherapeutic treatment for decades. However, platinum-resistant disease will recur in many cancers, including the majority of ovarian cancer cases. Thus, ovarian cancer can become a chronic, life-debilitating disease with limited options of therapy. Our research will focus on treating therapy-resistant cancers, primarily chronic therapy-resistant ovarian cancer.

Recent research demonstrates that therapy-resistant cancer cells are vulnerable to a recently described iron-dependent cell death pathway known as ferroptosis. However, current ferroptotic activators (Erastin and RSL3) are unable to circulate throughout the body, therefore alternative inducers are required. Many reports have shown that iron oxide nanoparticles can be cytotoxic to human cancer cells. Therefore, the use of such particles may be utilised in the treatment of ovarian cancer and other cancer types.

We hypothesise that targeting therapy-resistant cancer cells with iron oxide nanoparticles will induce ferroptotic cell death. The aim of this research project is to expand on current research and explore the link between iron nanoparticles and ferroptotic cell death.
Research methods to be undertaken will include 3D cell culture, confocal and fluorescent microscopy, PCR, immunoblotting and liquid chromatography-tandem mass spectrometry, using nanomaterials; such as ferumoxytol (superparamagnetic iron oxide nanoparticle (SPION)).

EPSRC Research Areas:

Therapeutics and nanomedicine

Publications

10 25 50