Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeted drug delivery achieved with nanoparticle-aptamer bioconjugates

02.11.2005


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
Further information:
http://www.fecs.be/emc.asp?pageId=10&Type=P

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>