doi:10.1038/nindia.2015.157 Published online 25 November 2015
Researchers have synthesized a composite core–shell nanofibrous scaffold that can slowly deliver a suicide gene and a prodrug to lung cancer cells1. The suicide gene encodes an enzyme that converts the prodrug into a toxic compound that kills cancer cells. This scaffold is expected to lead to an effective lung cancer therapy.
Suicide gene therapy delivers a suicide gene and a prodrug to target cells. The gene encodes a non-toxic functional enzyme, which converts the prodrug into a toxic compound that kills the target cells. Nanofibres can deliver a host of bioactive molecules such as drugs, DNA, proteins and nanoparticles, but their use in suicide gene therapy had not been studied previously.
The researchers used polymers to prepare the composite core–shell nanofibrous scaffold that had an outer shell and an inner core. The scientists loaded the outer shell with a suicide gene and the inner core with the prodrug 5-fluorocytosine. They then probed the scaffold’s efficiency to deliver and release the gene and prodrug to lung cancer cells.
After 32 hours, the scaffold released almost 85 per cent of the gene-containing shell and 65 per cent of the prodrug-containing core. After three days, the scaffold released almost 91 per cent of the prodrug, which was converted into toxic by-products by an enzyme encoded by the suicide gene inside the cancer cells. These toxic by-products killed the cancer cells by activating various genes and enzymes that destroy cancer cells in a controlled way.
1. Sukumar, U. K. et al. Bioactive core−shell nanofiber hybrid scaffold for efficient suicide gene transfection and subsequent time resolved delivery of prodrug for anticancer therapy. ACS Appl. Mater. Interfaces 7, 18717–18731 (2015)