Targeted drug delivery achieved with nanoparticle-aptamer bioconjugates
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.
In what marked the first-ever synthesis of a nanoparticle-aptamer bioconjugate, the nanoparticles were conjugated to RNA aptamers that bind to the prostate specific membrane antigen (PSMA) – a well known marker for prostate cancer which is over-expressed on certain prostate epithelial cells. Experimental results described at ECCO 13 show that these bioconjugates successfully and selectively adhered to PSMA-positive prostate cancer cells, while PSMA-negative cells were not targeted. This prostate cancer targeting was modeled using a microfluidic device and shown to occur under physiological fluid flow conditions that are present in systemic microvasculature, making their use after intravenous administration therapeutically relevant. The investigators also used high magnification microscopy and 3-D image reconstruction to study the localisation of the bioconjugates after incubation with the prostate cancer cells and confirmed that the particles were rapidly internalised into the targeted cells – an important fact since the payload of nanoparticles may be released inside the cancer cells in a regulated manner over an extended period of time.
The study principle investigator Dr Omid Farokhzad from Harvard Medical School, USA, commented, “Our tumour reduction data in mice using bioconjugates which have the chemotherapeutic agent, docetaxel, encapsulated within the nanoparticles are remarkably promising. In close collaboration with Dr. Robert Langer at MIT, we are continuing to test and optimise our vehicles in larger animal models of prostate cancer with the goal of one day using them on patients with hormone refractory prostate cancer where the current therapeutic modalities are far from adequate.”
These results mark the first ever example of targeted drug delivery using nanoparticle-aptamer bioconjugates. Significantly, the drug delivery was highly specific. Uptake of particles was not seen to be enhanced in cells which did not express the PSMA protein, indicating a selective tumour-targeting action.
“These bioconjugates represent an exciting prospect in the advancing field of cancer nanotechonology and hold significant promise for future cancer treatment,” remarked Dr Farokhzad. “Through modification of the controlled-release polymer system or tweaks to the aptamer targeting group it may be possible to produce a diverse range of specific and selective bioconjugates. In this way, drug delivery ‘vehicles’ can be made to target a myriad of important human cancers. The application of nanotechnology to cancer therapy is expected to result in future therapeutic modalities that are superior to our current approach. Importantly, this is no longer a farfetched science. Nanoscale drug delivery vehicles are getting closer to clinical realisation."
Kirsten Mason | alfa
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...