Why the Shape of Nanoparticles Matters


QDOTS imagesCAKXSY1K 8(Nanowerk News) Conventional treatments for diseases  such as cancer can carry harmful side effects—and the primary reason is that  such treatments are not targeted specifically to the cells of the body where  they’re needed. What if drugs for cancer, cardiovascular disease, and other  diseases can be targeted specifically and only to cells that need the medicine,  and leave normal tissues untouched?  
A new study involving Sanford-Burnham’s Erkki Ruoslahti, M.D.,  Ph.D., contributing to work by Samir Mitragotri, Ph.D., at the University of  California, Santa Barbara, found that the shape of nanoparticles can enhance  drug targeting. The study, published in Proceedings of the National Academy  of Sciences (“Using shape effects to target antibody-coated  nanoparticles to lung and brain endothelium”), found that rod-shaped  nanoparticles—or nanorods—as opposed to spherical nanoparticles, appear to  adhere more effectively to the surface of endothelial cells that line the inside  of blood vessels.
“While nanoparticle shape has been shown to impact cellular  uptake, the latest study shows that specific tissues can be targeted by  controlling the shape of nanoparticles. Keeping the material, volume, and the  targeting antibody the same, a simple change in the shape of the nanoparticle  enhances its ability to target specific tissues,” said Mitragotri.
“The elongated particles are more effective,” added Ruoslahti.  “Presumably the reason is that if you have a spherical particle and it has  binding sites on it, 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  that is in contact with the surface of the endothelial cells. More of the  antibodies that coat the nanorod can therefore bind receptors on the surface of  endothelial cells, and that leads to more effective cell adhesion and more  effective drug delivery.
Testing targeted nanoparticles
Mitragotri’s lab tested the efficacy of  rod-shaped nanoparticles in synthesized networks of channels called “synthetic  microvascular networks,” or SMNs, that mimic conditions inside blood vessels.  The nanoparticles were also tested in vivo in animal models, and separately in  mathematical models.
The researchers also found that nanorods targeted to lung tissue  in mice accumulated at a rate that was two-fold over 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 already used in some cancer 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 developed small chain molecules called peptides  that can be used to target drugs to tumors and atherosclerotic plaques.
Promising results
“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.
Source: Sanford-Burnham Medical Research Institute 

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