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Old 06-26-2007, 06:48 PM
Dross Dross is offline
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Default Nanoparticles carry chemotherapy drug deeper into solid tumors

Nanoparticles carry chemotherapy drug deeper into solid tumors

A new drug delivery method using nano-sized molecules to carry the chemotherapy drug doxorubicin to tumors improves the effectiveness of the drug in mice and increases their survival time, according to a study published online June 26 in the Journal of the National Cancer Institute.

In the past, similar drug carriers have improved targeted delivery of the drugs and reduced toxicity, but they sometimes decreased the drugs ability to kill the tumor cells. Using a new drug carrier, Ning Tang of the Chinese Academy of Sciences in Beijing and colleagues compared tumor growth and survival in mice that were given doxorubicin in the nanocarriers or on its own.

Doxorubicin delivered by nanocarriers was more effective in preventing tumor growth than free doxorubicin, and the mice receiving this treatment method lived longer and had fewer toxic side effects.

Encapsulation of doxorubicin increased its accumulation and penetration in tumors in terms of both the percentage of cells that were reached by the drug and the intracellular levels that were attained, the authors write.

In an accompanying editorial, Matthew Dreher, Ph.D., of the National Institutes of Health in Bethesda, Md., and Ashutosh Chilkoti, Ph.D., of Duke University in Durham, N.C., discuss the future of drug delivery, which they think should focus on three important research areas, drug combinations, targeting, and integration.

The study by Tang [and colleagues] is a simple but effective demonstration of the benefits of integration of a drug with an appropriate carrier to yield a striking gain in efficacy, the authors write. May the days of pharmacological missiles that miss their target and friendly fire that kills patients soon be over!

Last edited by gdpawel : 06-16-2013 at 11:35 AM. Reason: posted full article on forum board
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Old 06-16-2013, 11:39 AM
gdpawel gdpawel is offline
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Default Nanoparticles Deliver Targeted Therapies With Fewer Harmful Side Effects

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 Medical Research Institute'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, 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.

References:

We acknowledge support from a California Institute of Regenerative Medicine Fellowship, a National Science Foundation (NSF) Graduate Research Fellowship under Grant DGE-1144085, and the Materials Research Science and Engineering Centers Program of the NSF under Award Division of Materials Research 1121053.

The study was co-authored by Poornima Kolhar, UC Santa Barbara; Aaron C. Anselmo, UC Santa Barbara; Vivek Gupta, UC Santa Barbara; Kapil Pant, UC Santa Barbara; Balabhaskar Prabhakarpandian, UC Santa Barbara; Erkki Ruoslahti, Sanford-Burnham and UC Santa Barbara; and Samir Mitragotri, UC Santa Barbara.

Citation: Sanford-Burnham Medical Research Institute. "Novel Targeted Therapies With Fewer Harmful Side Effects." Medical News Today. MediLexicon, Intl., 12 Jun. 2013.
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