Synchronised delivery for DNA and drugs
26 September 2006
Polymer capsules that can simultaneously deliver drug molecules and DNA into a cell could boost the power of cancer treatments, scientists say.
The capsules are biodegradable nanoparticles that have an internal hydrophobic cavity that can hold drug compounds. In contrast, the outer shell of the capsule is positively charged and can bind DNA or RNA.
Previously, scientists have used viruses as gene delivery systems, forcing them to infect target cells with a corrective strand of DNA. If the treatment is successful the new gene is incorporated into the cell, correcting or enhancing the genetic code. Obeying these new instructions, the cell will start to make proteins to cure the illness, for example.
But there are limitations to this strategy. Viral manipulation at such a fundamental level is challenging, and there are still safety concerns about using viruses in this way. Alternative approaches have hidden the DNA inside soft self-assembled nanostructures to smuggle it into the cell.
The new nanocapsules go one better by carrying a double-pronged attack to cancer cells. Yi-Yan Yang from the Institute of Bioengineering and Nanotechnology, Singapore, and colleagues, built the capsules using a mixture of poly(N-methyldietheneamine sebacate) (PMDS) and a cholesterol-carrying monomer. This produced a molecular chain that self-assembled into a sphere with a hydrophobic internal cavity, lined with cholesterol molecules.
The scientists tested their capsules by loading them with paclitaxel (Taxol) and short strands of interfering RNA (siRNA), and tested the delivery vehicle on human breast cancer cells.
They found that more cells died when the two components were delivered simultaneously than if they arrived separately, possibly because the siRNA made the cells more sensitive to paclitaxel. 'These nanoparticles would have a great potential for co-delivering anticancer drugs and genes for improved cancer therapy,' the team suggest. The synergistic effect between drug and gene may also help to reduce the dose of anticancer treatments, they add.
Y Wang et al Nat. Mater. 2006, DOI:10.1038/nmat1737
Biodegradable polymers being developed in Atlanta, US, offer numerous advantages over current drug delivery systems, say researchers.