Feb 24, 2011
Nanocarrier delivers drugs to cancer cells
Microcapsules can be used to deliver siRNA to cancer cells and so help inhibit the growth of tumours, say researchers in Australia and Italy. The capsules hold a large payload of drugs compared to other nanocarriers and are easy to engineer.
Small interfering RNAs (siRNAs) are double-stranded RNA molecules that show promise for treating a variety of diseases because they prevent certain proteins from being produced in a biological cell. However, siRNAs are difficult to deliver to a target site, such as a tumour, and are quickly degraded in the blood stream. They also require a carrier to help them cross the cell membrane.
The new microcapsules, designed by Frank Caruso and colleagues of the University of Melbourne, are based on layer by layer assembly to create drug delivery vehicles that have nanometre-thin polymer walls. The capsules are made of a multi-layered thin polymer film assembled around a sacrificial template.
Caruso and colleagues began by immersing the template particles in a polymer solution, whereby the polymers adsorb onto the surface of the particles, forming a layer a few nanometres thick. Once the excess of this polymer had been washed away, the particles were immersed in another, complementary, polymer solution and a new polymer layer was adsorbed. The researchers repeated this process until the desired thickness had been achieved.
"The simplest film of this type is made of positively and negatively charged polymers, but in this case, the film is assembled using hydrogen bond interactions and then cross-linked with a cleavable bond that can be biodegraded," explained team member Alisa Becker.
The siRNA itself can either be loaded into the template at the start of the assembly process or into the formed capsule at the end. The capsules show interesting properties, such as being able to withstand the oxidising conditions of the blood stream. They also degrade in the reducing environment of a biological cell and can hold a large payload of siRNA.
Caruso's team found that the capsules can be used to slow down the growth of prostate cancer cells in vitro. Cancer cells contain a protein, called survivin, that prevents the cells from dying once they have reached their "use-by date". The siRNA delivered by the capsules can stop the overproduction of this protein, and the cell thus dies at the normal time.
"In the future, such a technology may eliminate or reduce the amount of chemotherapy drugs needed to destroy a tumour," Becker told nanotechweb.org.
Without the microcapsules, the siRNA would degrade in the bloodstream long before it reached the target cancer cells. Another advantage of the capsules is that they can easily be engineered to be thicker or thinner, with varying permeability, surface chemistry, size and biodegradability.
The team, which includes researchers from the Istituto Nazionale dei Tumori in Milan and the University of Roma Tor Vergata, is now busy modifying the surface of the capsules for targeted drug delivery. It is also optimising intracellular uptake and degradation, carrying out in vivo studies and characterising how the cancer cells react to the microcapsules. One challenge that needs to be overcome is cancer cell "autophagy" – where cancer cells seem to self-digest as a protective mechanism in the presence of the microcapsules.
The present results were published in ACS Nano.
About the author
Belle Dumé is contributing editor at nanotechweb.org