Nanorods found better than spherical nanoparticles for targeted drug delivery
June 12, 2013
Conventional treatments such as drugs for diseases such as cancer and cardiovascular disease can carry harmful side effects, mainly because the treatments are not targeted specifically to the cells of the body where they’re needed.
Now a new study has found that rod-shaped nanoparticles (nanorods) — as opposed to spherical nanoparticles — appear to adhere more effectively to the surface of endothelial cells (which line the inside of blood vessels), allowing for drug targeting to specific type of cells.
“The elongated particles are more effective,” said Sanford-Burnham Medical Research Institute’s Erkki Ruoslahti, M.D., Ph.D. “Presumably the reason is that … the curvature of the sphere allows only so many of those binding sites to interact with membrane receptors on the surface of a cell.”
In contrast, the elongated nanorods have a larger surface area in contact with the surface of the endothelial cells. So more of the antibodies that coat the nanorod can bind to receptors on the surface of endothelial cells, and that leads to more effective cell adhesion and more effective drug delivery.
Testing targeted nanoparticles
UC Santa Barbara’s Dr. Samir Mitragotri’s lab tested the efficacy of rod-shaped nanoparticles in synthesized networks of channels called “synthetic microvascular networks” (SMNs), which mimic conditions inside blood vessels. The nanoparticles were also tested in vivo in animal models, and separately in mathematical models.
The researchers found that nanorods targeted to lung tissue in mice accumulated twice as fast as nanospheres engineered with the same targeting antibody. Also, enhanced targeting of nanorods was seen in endothelial cells in the brain, which has historically been a challenging organ to target with drugs.
Nanoparticles have been studied as vessels to carry drugs through the body. Once they are engineered with antibodies that bind to specific receptors on the surface of targeted cells, these nanoparticles also can, in principle, become highly specific to the disease they are designed to treat.
Ruoslahti, a pioneer in the field of cell adhesion — how cells bind to their surroundings — has also developed small chain molecules called peptides that can be used to target drugs to tumors and atherosclerotic plaques.
“Greater specific attachment exhibited by rod-shaped particles offers several advantages in the field of drug delivery, particularly in the delivery of drugs such as chemotherapeutics, which are highly toxic and necessitate the use of targeted approaches,” the authors wrote in their paper.
The studies demonstrate that nanorods with a high aspect ratio attach more effectively to targeted cells compared with spherical nanoparticles. The findings hold promise for the development of novel targeted therapies with fewer harmful side effects.
The study was supported by a California Institute of Regenerative Medicine Fellowship, a National Science Foundation (NSF) Graduate Research Fellowship, and the Materials Research Science and Engineering Centers Program of the NSF.