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Appetite for Aptamers: MIT and Harvard might lead charge to targeted drug delivery via nanoparticle-aptamer bioconjugate
December 2005
by Jeffrey Bouley  | 


CAMBRIDGE, Mass.—The Massachusetts Institute of Technology (MIT) and Harvard University recently announced that they are receiving five-year funding from the National Cancer Institute, to the tune of $20 million, for the MIT-Harvard Center of Cancer Nanotechnology Excellence. Closely following this announcement was the presentation of recent research at November's 13th European Cancer Conference regarding the use of nanoparticle-aptamer bioconjugates for drug delivery, which was spearheaded by MIT and the Harvard Medical School.
Although the two events may not seem intimately entwined at first glance, the research highlighted in Paris will likely play a part in strongly encouraging at least one line of research at the new center: targeted drug delivery by pairing nanotechnology and aptamers.
Principal investigators for the new cancer nanotech center will be Harvard Medical School professor Dr. Ralph Weissleder and MIT professor Dr. Robert Langer, the latter having been directly involved in the nanoparticle-aptamer bioconjugates research that was noted at the European Cancer Conference. One of the center's researchers, Dr. Omid Farokhzad—a Harvard Medical School professor and a former postdoctoral fellow under Langer—was lead researcher for the nanoparticle-aptamer study cited in Paris.
Thanks to the attention Langer and Farokhzad's work got in November, drug discovery research worldwide should be looking more closely at aptamers for various applications. But aptamers as a therapeutic tool may get a particular nudge in the Cambridge, Mass., area with the two researchers working together at the new Center of Cancer Nanotechnology Excellence. Dr. Langer says aptamers probably won't end up being the biggest area of research for the new center, but he describes them as a very exciting area that the center will pursue, in part because aptamers have the potential to act as targeting molecules directing the delivery of nanoparticles to tumor-antigens present on the surface of cancer cells.
"I see this work in aptamers as opening the doors for all kinds of new targeting strategies in drug discovery and drug delivery using nanoparticles," he notes.
The investigators at the center will pursue five major cancer research projects—along with any number of smaller pilot projects over the next several years—spanning the entire spectrum of nanotechnology applications, from fabricating nanoparticles for targeted delivery of therapeutic drugs and imaging agents to implanting tiny sensors for early detection and cancer monitoring. One of those five major projects, led by Langer and Farokhzad, will focus on using nanoparticles to transport time-release anticancer drugs directly to prostate cancer cells.
"One of the problems with cancer therapy is that it goes everywhere in the body," often causing toxic side effects, Langer says, and this approach would help reduce such problems. "We proposed making nanoparticles with units attached to them—homing devices, if you will—that would target only cancer cells," he added.
This is probably one of the areas where aptamers will get the most play at the Center of Cancer Nanotechnology Excellence, since Langer and Farokhzad's earlier nanoparticle-aptamer bioconjugates research used aptamers as those "homing devices" to provide targeted delivery of time-released drugs at the site of cancer.
"These bioconjugates represent an exciting prospect in the advancing field of cancer nanotechnology and hold significant promise for future cancer treatment," says 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, he adds, with therapeutic modalities that are far superior to current approach.
"Importantly, this is no longer a farfetched science," Farokhzad says. "Nanoscale drug delivery vehicles are getting closer to clinical realization."
Meet the Aptamers
In the drug discovery world, aptamers are nothing new. Aptamer-based drugs are still a fledgling area, but aptamers themselves have already found homes in the labs of various researchers who have achieved success using them for target validation and drug discovery. For example, aptamers have been used in cell-based knockdown studies of intracellular and extracellular target proteins and drug screening with inhibitory aptamers, which have helped generate small-molecule hits with biological activity.
As to what thes helpful tools are specifically: An aptamer is any small synthetic nucleic acid ligand—a short DNA or RNA fragment—that can bind to a particular target molecule, such as a protein or metabolite. In this way, they are analogous to monoclonal antibodies. Aptamers tend to show strong inhibition of protein function, owing to their  small molecule-like binding characteristics, and they are considered good candidates for molecular imaging applications because of such features as rapid blood clearance and tumor penetration. They are generated in an automated in vitro process and can be synthesized and modified using standard chemistry.
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