New nanodevice prevents drug resistance

4 March 2015

A new device has proven effective for preventing cancer cells becoming resistant to drug intervention.

This could be crucial for treatment as chemotherapy can often shrink tumours but they soon become resistant to therapy, meaning the mass soon grows back. The new device, developed by a team at Massachusetts Institute of Technology (MIT), can help overcome this as it blocks the gene that enables drug resistance. In addition, it then triggers another dose of chemotherapy to the vulnerable tumours.

Containing gold nanoparticles embedded in a hydrogel, the device is able to either be injected or implanted into the tumour site, and could be used to disrupt any gene involved in the disease.

"You can target any genetic marker and deliver a drug, including those that don't necessarily involve drug-resistance pathways. It's a universal platform for dual therapy," said Dr Natalie Artzi, a research scientist at MIT's Institute for Medical Engineering and Science (IMES).

Dr Artzi, who is also an assistant professor at Harvard Medical School and senior author of the paper, tested the approach using a type of human breast tumour known as a triple negative tumour, which are usually very challenging to treat.

Along with her team, she found the new device was able to block the gene for multidrug resistant protein 1 (MRP1), and then deliver another boost of a chemotherapy drug 5-fluorouracil. This reduced the tumours by 90 per cent in laboratory experiments in just two weeks.

Published in the Proceedings of the National Academy of Sciences (PNAS) journal, the study could overcome one of the most challenging areas of modern cancer treatment.

"Drug resistance is a huge hurdle in cancer therapy and the reason why chemotherapy, in many cases, is not very effective," said João Conde, an IMES postdoc and lead author of the paper.

MRP1 is a gene that can help tumours become resistant to cancer drugs as it fights off the drugs. To overcome this, the team developed gold nanoparticles coated with strands of DNA, which complemented the sequence of MRP1 messenger RNA, which instructs the cell.

The strands or nanobeacons close up until they find an appropriate mRNA sequence inside a cancer cell, where it unfolds and attaches to the mRNA. This stops it from generating more molecules of the MRP1 protein. 

As the DNA strands unfold, molecules of 5-fluorouracil are released and the drug is then able to attack the tumour, as MRA is no longer there to remove it.

The team say that silencing the gene means the cell is no longer resistant to that drug, so the drug regains its efficacy.

This novel approach could be used to deliver any type of drug or gene therapy to a specific gene involved in cancer, the researchers say, with studies now in progress to try the same method on the genes that trigger gastric tumour metastasis in the lungs.

Posted by Phillip Briggs

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