'Nested' nanoparticles increase efficiency of drug delivery
that finally allows nanomedicine to fulfil its potential.
University of Texas researchers believe that by encasing their drugs in a series of nanoparticles they can produce a highly targeted treatment that bypasses the body's immune defences which have typically plagued other nanotechnology therapies. These defences protect the body from foreign bodies that enter the bloodstream, including therapeutic nanoparticles. The different levels of attack include enzymes in the blood corrode the particles and microphage cells that actively attack and destroy the particles and remove them from the bloodstream. The drug must then penetrate the vessel walls to reach deep inside the tumour. These defences are so effective that on average just one out of every 100,000 drug molecules actually end up in the area they were meant to be targeting. In the past it had been difficult to find particles that could both penetrate these "biobarriers" and effectively find and target the correct tumour cells. Mauro Ferrari's multistage delivery system overcomes these defences using a series of nanoparticles, contained one inside the other. As it passes through each barrier the drug sheds a shell to reveal a new particle that is best suited to the next line of immune defence. "We realised that if the barriers are sequential, then the drug delivery must also be sequential," Mauro Ferrari, the lead researcher, told in-PharmaTechnologist.com. "It's multistage, like a spaceship going to the moon that is actually made of many rockets for the different stages of its journey." The "mother ship" that faces the first line of defence takes the form of a mesoporous silicon particle, designed to avoid attack by the microphages and which can withstand enzyme corrosion. "Silicon is fully biodegradable to a rate that can be carefully controlled, and the degradation products are harmless and produced in quantities much lower than the average dietary intake. In addition, we know how to manufacture its size, shape, and charge density to a great variability - as used in the microelectronics industry," explained Ferrari. Because of this, scientists can successfully design the particles so they preferentially fix firmly to the endothelial cells that line the blood vessels surrounding a tumour. The particles may also secrete a toxin that causes the vessel wall to part slightly to allow the particle to permeate further into the tumour itself. Once in their desired position, the silicon particles can release quantum dots or carbon nanotubes - both of which act as contrast agents for imaging applications. The carbon nanotubes can also be stimulated to produce heat, which itself could be used as a therapy. These particles can also be used to deliver other therapeutic agents, to achieve high concentrations within the tumour without needing to increase the actual dosage of the drug. Ferrari is currently investigating the possibility of using the particles to deliver short interfering RNA (siRNA) molecules that could silence messenger RNA within a tumour cell to stop it reproducing. Ferrari presented his research in the March issue of Nature Biotechnology.