46 nanotimes News in Brief
Cancer Therapy // The Best Shape for Cancer-Fighting Nanoparticles © Based on Material by TMHRI, Houston, TX, USA
As the field of nanomedicine matures, an emerging point of contention has been what shape nanoparticles should be to deliver their drug or DNA payloads most effectively. A pair of new papers by scientists at The Methodist Hospital Research Institute (TMHRI, US) and six other institutions suggests these microscopic workhorses ought to be disc-shaped, not spherical or rod-shaped, when targeting cancers at or near blood vessels.
"The vast majority – maybe 99% – of the work being done right now is using nanoparticles that are spherical," said TMHRI biomedical engineer Paolo Decuzzi, Ph.D., principal investigator for both projects. "But evidence is showing there may be better ways to get chemotherapy drugs to the site of a vascularizing cancer."
Despite their popularity, there are problems with sphere-shaped nanoparticles. They‘re small, and can‘t deliver a lot of drugs when they finally reach their targets. And they‘re also more likely to get pushed downstream by blood‘s powerful flow.
"The small surface exposed by spherical nanoparticles to the blood vessel walls – theoretically a single point – in the tumor tissue cannot support stable, firm adhesion and they are easily washed away. And this hampers their effective accumulation within the diseased tissue," Decuzzi said. "So a number of laboratories have been asking, how can we maximize the accumulation of nanoparticles in the diseased tissues? Is there a better shape?"
In the August 2012 Biomaterials*, Decuzzi and coauthors show that at different, biologically relevant flow speeds, disc-shaped nanoparticles were less likely to get pushed off their targets than rod-shaped nanoparticles – another shape previously proposed as an alternative to spheres. The ideal size was 1,000 by 400nm (diameter by thickness). The experiments were conducted in vitro and confirmed by computational modeling. Spherical nanoparticles are built around the drug payload in a free, three-dimensional fashion through self-assembly. The particle grows uniformly in all directions, forming a spherical – or nearly spherical – nanoparticle. The Methodist nanomedicine group, led by TMHRI President and CEO Mauro Ferrari, Ph.D., has developed a completely different technique. Disc-shaped nanoparticles are created with photolithographic technology, the same tools used to make the tiniest components in computers. Photolithography allows Ferrari, Decuzzi, and colleagues to specify the size, shape and surface properties of the nanoparticles with a great deal of accuracy. The nanoparticles are built with sponge-like holes through them, which is where the drugs are loaded. "We can change the size, shape, and surface properties – '3S' parameters – of the particles independently," Decuzzi said. "It is a very powerful technique."
The nanoparticles are built with silicon, and biologically relevant molecules are later attached to the outside to improve binding to target cells and to delay destruction by the immune system. Silicon has an extremely low toxicity profile at the doses typically used in humans and animal models. Decuzzi said silicon nanoparticles are readily broken down and removed from the body within 24 to 48 hours. The second paper published by Decuzzi and colleagues**, used mouse models to show that 1,000 by 400nm disc-shaped nanoparticles bind readily to and near melanoma cells, at 5% to 10% of the injected dose per gram organ – concentrations that are competitive with or better than those previously reported for spheroid nanoparticles. The researchers also showed 1000 by 400nm discs were least likely (than smaller or larger discs, or rods) to end up in the liver.
*Giulia Adriani, Marco Donato de Tullio, Mauro Ferrari, Fazle Hussain, Giuseppe Pascazio, Xuewu Liu, Paolo Decuzzi: The preferential targeting of the diseased microvasculature by disk-like particles, In: Biomaterials, Volume 33(2012), Issue 22, August 2012, Pages 5504-5513, DOI:10.1016/
j.biomaterials.2012.04.027:
http://dx.doi.org/10.1016/j.biomaterials.2012.04.027
**Anne L. van de Ven, Pilhan Kim, et al.: Rapid tumoritropic accumulation of systemically injected plateloid particles and their biodistribution, In: Journal of Controlled Release, Vol. 158, Issue 1, February 28, 2012, Pages 148-155, DOI:10.1016/j.jconrel.2011.10.021:
http://dx.doi.org/10.1016/j.jconrel.2011.10.021
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