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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>