Ground-breaking results from researchers at Harvard Medical School and Massachusetts Institute of Technology (MIT), USA, disclosed at the 13th European Cancer Conference (ECCO) in Paris have shown for the first time that targeted drug delivery is possible using nanoparticle-apatamer conjugates.
Nucleic acid ligands (referred to as aptamers) are short DNA or RNA fragments that can bind to target antigens with high specificity and affinity; analogous to monoclonal antibodies. In the field of cancer nanotechnology, aptamers have the potential to act as targeting molecules – directing the delivery of nanoparticles to tumour-antigens, present on the surface of cancer cells. In general terms, therapeutic nanoparticles (~50 – ~250 nanometer) are specially designed delivery vehicles that can encapsulate a drug within them and release the drug in a pre-determined and regulated manner which can vary from a sudden release to a slow release over a period of several years. Using prostate cancer as a model disease, proof of concept nanoscale targeted drug delivery vehicles were developed (1 nanometer = 0.000000001 meter), which can target prostate cancer cells with high specificity and efficiency. Once bound to prostate cancer cells, the nanoparticle/aptamer bioconjugates were internalised making it possible for their cytotoxic payload to get released directly inside the cancer cells. The combination of targeted delivery and controlled release of drugs at the site of cancer will likely result in "smart therapeutics" that are more effective, yet safer than what is available today.
As the initial step, researchers synthesised nanoparticles for controlled drug release made from a biocompatible and biodegradable PLA polymer system and encapsulated a fluorescently labeled model drug within them, in order to visualise nanoparticle uptake into target cells. The nanoparticles in question were designed for attachment to aptamers so that the binding properties of aptamers for targeting could be preserved. Additional design criteria consisted of the development of nanoparticles that demonstrated a long circulating half-life (meaning that they are not readily cleared by the body’s immune system) and nanoparticles that exhibited a strong preferential binding to targeted cancer cells.