Nanotechnology techniques can improve cardiovascular implant devices

Electronics-research-001(Nanowerk News) Jeong-Yeol Yoon, associate professor of agricultural and biosystems engineering, and Dr. Marvin Slepian, professor of cardiology and biomedical engineering, collaborated to test how nanotechnology-based techniques can be used to better facilitate adhesion between tissue and implanted devices.
“When we created the nanotexture surface, we thought it could be used as a sticky surface for the implants,” Yoon says.
Cell-substrate adhesion involves the interplay of mechanical properties, surface topographic features, electrostatic charge and biochemical mechanisms. By working at the nanoscale level, Yoon was able to maximize the physical properties of the underlying substrate in promoting adhesion.
But beyond simply creating a sticky surface, the researchers’ goal was to create a selectively sticky surface, favoring endothelial cell attachment, without favoring platelet attachment, Slepian says.
The connection between Yoon, a specialist in biosensors and nanotechnology from the College of Agriculture and Life Sciences, and Slepian, co-founder and chief scientific officer of artificial-heart manufacturer SynCardia, came about by chance. A graduate student in Yoon’s lab met Slepian through their shared interest in bicycling.
“It’s very rare for the agriculture people to work with the cardiovascular people in the medical school,” Yoon says.
But their research specialties clicked.
One particular challenge to overcome in cardiovascular implants is the potential for devices – such as stents placed inside coronary arteries – to become detached as a result of blood flow, Yoon says.
“We’re particularly focused on the cardiovascular applications because there’s a blood flow involved and our system is very good when there’s a flow situation,” Yoon says.
The results of the study, published in the journal Advanced Healthcare Materials (“Nanowell-Trapped Charged Ligand-Bearing Nanoparticle Surfaces: A Novel Method of Enhancing Flow-Resistant Cell Adhesion”), reveal that the researchers’ strategy leads to enhanced endothelial cell adhesion under both static and flow conditions.
The adhesive properties derive from optimized surface texturing, electrostatic charge and cell adhesive ligands (molecular binding substances) that are uniquely assembled on the substrata surface as an ensemble of nanoparticles trapped in nanowells.
“There are lot of other people out there who use nanotechnology for improving the implants, but this is stronger than other adhesive methods using nanotechnology,” Yoon says.
“Obviously it can be used for everything else – lungs, digestive track and other systems. There are lots of other opportunities we haven’t explored,” he says.
The research is a perfect fit for Advanced Healthcare Materials, a new journal that spun off from the longstanding Advanced Materials journal.
“The use of the materials for the health care applications is probably the hottest area in materials science and engineering,” Yoon says. “We believe the journal will become even stronger than the mother journal.”
Just as the new journal marks an exciting intersection of disciplines, Yoon says the environment at the UA encourages such interdisciplinary approaches.
“I joined the University of Arizona because there are so many interdisciplinary activities going on. I see a lot of collaboration between departments in the same college at other universities, but at the University of Arizona, the environment is more open and you see collaboration across colleges,” Yoon says.
Slepian agreed, saying the pair has already filed grant applications for future work together.
“It has been fun and exciting to have an interdisciplinary collaborator,” he says.
Source: University of Arizona

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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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