If successful, the research teams believe this could create opportunities for the creation of new drug delivery vehicles that house innovative anticancer therapies that so far have failed to breach the human body’s defences.
The use of RNA interference (RNAi) is one such innovation. Since its potential for silencing genes was discovered in 2006 it has been considered a powerful approach for silencing genes associated with conditions including cancer. However, in vivo RNAi delivery has remained a challenge due to lack of safe, efficient, and sustained systemic delivery.
Mauro Ferrari, of the University of Texas Health Sciences Centre in Houston, US, led a research team that developed lipid-based nanoparticles that encapsulated siRNA molecules.
Earlier work by Dr Ferrari’s team had already shown that these lipid nanoparticles could deliver siRNA molecules to tumours. However, achieving a therapeutic effect in tumour-bearing mice required twice-weekly injections for many weeks.
To reduce the number of injections needed, Dr. Ferrari and his team loaded their nanoparticle-siRNA construct into the pores of biocompatible nanoporous silicon particles. This drug delivery vehicle was then injected into mice with human ovarian tumours.
Later examinations of the mice found shrunken tumours with the siRNA agent still showing efficacy. More importantly, the researchers found toxicities to be minimal or in some cases, non-existent.
"The multistage delivery system is revolutionary in that it allows the therapeutic payloads to cross the biological barriers in the body and reach their target,” said Ferrari, who is also the chairman of the Department of NanoMedicine and Biomedical Engineering at The University of Texas Medical School.
“It further helps release agents over long periods of time directly into the bloodstream, which is unprecedented."
The results of the paper provide the first indication of the therapeutic advantages of the multistage delivery system in animal models of cancer. However, several more years of tests are likely to remain before the drugs could be approved for widespread use.
"This is an exciting development because RNA interference has worked well in an animal model but has such a short half-life that it requires frequent delivery,” said Dr. Anil Sood, Anderson's Departments of Gynaecological Oncology and Cancer Biology.
“A three-week dosing period is much closer to the sustained dosing needed to properly test this therapy in clinical trials."