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One of the ways in which cancer cells evade anticancer therapy is by producing a protein that pumps drugs out of the cell before these compounds can exert their cell-killing effects. A research team at Northwestern University has found that biocompatible iron oxide-titanium dioxide nanoparticles can bypass this pump and enable DNA-damaging anticancer drugs to reach the cell nucleus.
Gayle Woloschak, a member of the Northwestern University Center for Cancer Nanotechnology Excellence, led the research team that developed this nanoparticle. She and her collaborators reported their findings in the journal Cancer Research.
The goal of this work was two-fold: identify a nanoparticle that would overcome pump-related drug resistance which could simultaneously serve as a tumor imaging agent. The researchers chose a nanoparticle with an iron oxide core surrounded by a titanium dioxide shell. The iron oxide core serves as a powerful magnetic resonance imaging (MRI) contrast agent, while the titanium dioxide shell can bind to anticancer agents such as doxorubicin through a chemical bond that will break in the acidic conditions inside a cancer cell.
The investigators treated drug-resistant ovarian cancer cells with a doxorubicin-loaded nanoparticle and showed that the nanoparticle was readily transported into the cells. More importantly, the nanoparticles released their drug payload, enabling doxorubicin to reach the cell nucleus. Doxorubicin kills cells through a process that involves binding to DNA in the nucleus. When compared to doxorubicin alone, the resistant cells accumulated up to 6 times more drug then when administered using the nanoparticle-drug combination. Interestingly, the researchers found that when they co-administered even empty nanoparticles (no doxorubicin) with transferrin, a molecule involved in iron transport, they saw increased cell uptake of transferrin. This observation is important since many research groups are developing nanoparticles that incorporate transferrin on the surface to stimulate cell uptake. In this scenario, it could be beneficial to co-treat with this type of empty particle.
About The National Cancer Institute (NCI)
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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