Resistance to treatment with chemotherapeutic drugs is a major complication in clinical oncology and is one of the most common treatment limitations in patients with reoccurring cancers. Researchers have developed nanoparticle (NP)-based drug delivery systems designed to overcome drug resistance in cancer cells mainly by avoiding the activation of efflux pumps in these cells. According to a study published in the scientific journal Biomaterials, these nanoparticles filled with chemotherapeutic have shown to be effective.
Nanoparticles are just as small, or even smaller, than many blood proteins. They can therefore pass through the walls of healthy and cancer cells, which make them interesting carriers of drugs against cancer and other diseases.
Nanoparticles carrying the drug to kill resistant cancer cells by controlling where in the cancer cell they delivered their payload.
Biodegradable plastics
In the study, researchers from Karolinska Institutet have shown that nanoparticles made from biodegradable plastics. These polyester-based hyperbranched dendritic-linear (HBDL)-based nano particles
can overcome drug resistance in breast cancer cells. Such resistance is especially common in relapsing cancer patients and depresses, even neutralises the effect of the therapy against the tumour in many instances.
In their experiments, the researchers used breast cancer cells that responded poorly to drugs owing to their high concentrations of the enzyme microsomal glutathione S-transferase-1 (MGST-1). Abnormally high levels of MGST-1 have been associated with poor responses to several cancer drugs. The team treated the resistant breast cancer cells with nanoparticles filled with doxorubicin, a chemotherapeutic used clinically to treat bladder, lung, ovarian and breast cancer, amongst others.
Harmless
“Our experiments on cultivated cells showed that the particles themselves are harmless,” noted research team member Andreas Nystr?m, M.Sc,Ph.D, Associate Professor at the Institute of Environmental Medicine, Karolinska Institutet. “We made it possible for the nanoparticles carrying the drug to kill resistant cancer cells by controlling where in the cancer cell they delivered their payload. This improved the efficacy of the drug even at a much lower dose, which is important for limiting the adverse reactions to therapy.”
Nanoparticles can also be used to control where the drug is delivered in the body, and the team is now planning to equip them with targeting groups such as peptides or antibodies, that direct them to specific tumor cells to increase the uptake of the particles and their drug content by the tumour while sparing healthy cells.
For more information:
Zeng X, Morgenstern R, Nystr?m AMNanoparticle-Directed Sub-cellular Localization of Doxorubicin and the Sensitization Breast Cancer Cells by Circumventing GST-Mediated Drug Resistance. Biomaterials (corrected proof online 6 November 2013) [Article]
Photo: In their study published in Biomaterials (November 2013), Andreas Nystr?m and his colleagues at Karolinska Institutet show that nanoparticles can overcome drug resistance in breast cancer cells. Photo courtesy: Bildmakarna.
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