08 October 2012

Delivery of drugs to aging cells

Anti-aging Nanoparticles

NanoNewsNet based on ScienceDaily: Nanoparticles Against AgingA group of Spanish scientists has developed an intelligent nanodevice that lays the foundations for the development of new methods to combat aging.

The device consists of nanoparticles that can selectively release the necessary drugs in aging human cells. The range of its future potential use is very wide – from the treatment of diseases accompanied by degeneration of cells or tissues, such as cancer, Alzheimer's or Parkinson's disease, to accelerated aging of the body (progeria).

"The nanodevice we have developed consists of mesoporous nanoparticles with a galactooligosaccharide outer coating, which prevents the release of their payload and selectively opens only in cells in the stage of degeneration or aging cells. This nanodevice – proof of concept – demonstrates for the first time that certain chemicals can be released in these cells, and not in other cells," says one of its authors Ramon Martinez Manez, a researcher at the Center for Molecular Research and Technological Development (Centro de Reconocimiento Molecular y Desarrollo Tecnologico).

According to the head of the study, Jose Ramon Murguia, a researcher at the Institute of Molecular and Cellular Biology of Plants (Instituto de Biología y Celular de Plantas), aging is a physiological process aimed at destroying old or altered cells whose viability is threatened.

"When we are young, the mechanisms of aging prevent, for example, the appearance of tumors. The problem is that with age, aging cells accumulate in organs and tissues, disrupting their normal functioning. The destruction of these cells would slow down the development of diseases associated with aging. Our work shows that we can develop targeted therapy directed against such cells," Murgia comments on his understanding of the aging process and the possibilities of combating it.

So far, researchers have evaluated the effectiveness of the new nanodevice on primary cell cultures of patients with accelerated aging syndrome – congenital dyskeratosis. Such cultures are characterized by a high rate of aging and an increased level of the enzyme beta-galactosidase.

"Aging cells overexpress this enzyme, and we have developed nanoparticles that open in its presence, releasing their contents to destroy aging cells, prevent their deterioration, or even activate rejuvenation," Murgia explains.

Controlled intracellular release of molecules in aging cells is achieved using mesoporous silicon dioxide nanoparticles coated with galactooligosaccharide (galactooligosaccharide, GOS) molecules and containing payload molecules (shown in the diagram as purple spheres).

Galactooligosaccharide is a substrate for the biomarker of aging – the enzyme associated with aging beta-galactosidase (senescence-associated beta-galactosidase, SA-b-gal) – and allows nanoparticles to release the payload after entering cells with a high level of expression of SA-b-gal.

Figure from the article by Agostini et al. Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles, published in the journal Angewandte Chemie.

"There are a number of diseases associated with premature tissue aging, many of which develop in very young patients for whom there are no therapeutic alternatives, such as, for example, in the case of congenital dyskeratosis or aplastic anemia. Other diseases, such as idiopathic pulmonary fibrosis or cirrhosis of the liver, develop in adults. Our nanoparticles represent a unique opportunity to selectively deliver therapeutic compounds to damaged tissues and prevent the loss of their viability and functionality," explains Rosario Perona, one of the authors of the development, a researcher at the Institute of Biomedical Research (Instituto de Investigaciones Biomedicas).

In the near future, Spanish researchers plan to test the effectiveness of their device when loading nanoparticles with various therapeutic drugs, and also test it not on cell cultures, but on animal models.

"As far as we know, this is the first description of nanotherapy for aging cells. Despite the fact that there is a long way to go from these results to the possible destruction of aging cells or anti–aging therapy, we believe that our research can open up new ways to develop treatments for age-related diseases," says Martinez Manes.

According to Spanish scientists, the new nanodevice may also be useful in cosmetology – as a means of delivering drugs to combat wrinkles and aging of the skin, to protect against UV radiation or treat alopecia, since all these conditions are associated with the accumulation of aging cells in tissues.

Portal "Eternal youth" http://vechnayamolodost.ru08.10.2012

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