Chemotherapy is a common cancer treatment, using drugs to destroy cancer cells. However, cancer cells can develop resistance to chemotherapy drugs by developing “efflux pumps”, pumps in the cell membrane that work to actively expel the chemotherapy drugs from the tumor cells. Shana Kelley and her team in University of Toronto developed nanomaterials that can deliver drugs into cancer cells and suppress their drug resistance.

The drug-resistant cancer cells contain RNA that can be turned into proteins that form the efflux pumps. To target this RNA, Kelley’s team made two-layered nanomaterials consisting of gold nanoparticles encapsulated by a layer of small nanoparticles. Gold is used as the core nanoparticle because DNA easily binds to gold’s surface. Both nanoparticle layers are assembled using DNA as glue, and the DNA on the inner layer is specifically designed to bind the pump-forming RNA. The chemotherapy drug is loaded onto the outer layer’s DNA. Due to their small size, the nanomaterials can be taken up by the cells. The smaller nanoparticles in the outer layer will detach to expose the DNA-coated gold nanoparticles, which can specifically bind the pump-forming RNA, suppressing the formation of the efflux pumps. At the same time, the chemotherapy drug is released, afflicting the cancer cells.

While the study only tested the nanomaterials on cancer cells grown on a flat substrate, the researchers are planning to incorporate spatiotemporal control of the drug release in animal models. For example, the amount of the nanomaterials can be tuned for specific tumor sites, and the drugs can be encapsulated in dissolvable shells to control the timing of drug release. Future studies should investigate whether these nanomaterials affect normal cells and the nanomaterials’ stability in blood circulation, which are important factors when delivering chemotherapy drugs in the human.

Managing Correspondent: Anqi Zhang

Original journal article: Programmable Metal/Semiconductor Nanostructures for mRNA-Modulated Molecular Delivery. Nano Letters.

Image Credit: Wellcome Collection

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