| Posted: February 20, 2007 |
Nanoparticles rely on 'velcro effect' to target tumor cells |
|
(Nanowerk News) One of the basic tenets of targeted nanoparticle drug delivery is putting multiple targeting molecules on a nanoparticle surface will improve the ability of nanoparticles to stick to their targeted cell and deliver their drug cargos to the appropriate diseased cell. Now, work from one of the National Cancer Institute's Cancer Nanotechnology Platform Partnerships shows that a velcro-like process does indeed improve cell-specific targeting of nanoparticles to tumor cells.
|
|
Velcro owes its incredible sticking power to the power of large numbers of weak interactions ' any one hook on one piece of Velcro forms a weak connection to any one loop on its matching piece of Velcro, but when each of a dozen hooks binds to each of a dozen loops, the sum is a rugged connection. While any one hook-and-loop connection can break, the remaining connections remain, allowing the wayward pair to reconnect before the two pieces of Velcro separate.
|
|
Writing in the journal Chemistry and Biology ("The binding avidity of a nanoparticle-based multivalent targeted drug delivery platform"), a team led by James Baker, Jr., M.D., principal investigator of the University of Michigan-based DNA-linked Dendrimer Nanoparticle Systems for Cancer Diagnosis and Treatment program, showed that a similar process occurs when nanoparticles with multiple targeting molecules bind to a tumor cell. In their experiments, the researchers used a nanoparticle known as a dendrimer that contained multiple folic acid molecules on its surface. Folic acid, which binds to a protein, or receptor, found at high levels on the surfaces of many types of tumor cells, is considered one of the more promising tumor-targeting molecules being developed today.
|
|
The researchers set out to test which of two hypotheses best explains the observation that targeted nanoparticles are far more efficient at delivering drug molecules or imaging agents to tumor cells than when the targeting agent is attached directly to an individual drug molecule. One hypothesis holds that the Velcro mechanism is responsible for the superior delivery properties of targeted nanoparticles, while the second hypothesis credits cells with being able to more rapidly take up nanoparticles than individual drug molecules.
|
|
To test these hypotheses, the investigators created dendrimers with between zero and 15 folic acid molecules and then used several methods to test the particles' binding characteristics and rate of uptake by targeted cells. These experiments showed conclusively that dendrimers bound more tightly ' as much as 170,000-fold ' to the cells as the number of folic acids increased. In contrast, the rate of uptake of the various dendrimers did not change. Calculations suggested that five to six folic receptors can clump together on the surface of a cell to bind to a single dendrimer containing numerous folic acids.
|
