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Cynthia Aracely Alvizo-Baez

Title: Magnetic nanoparticles of chitosan for delivery trail expression and apoptosis in lungs induced by external magnetic field

Cynthia Aracely Alvizo-Baez

Universidad Autonoma De Nuevo Leon, Mexico

Biography

Graduated in Biology (2009). Master in Immunology (2012). PhD in Immunology (2016) from Universidad Autónoma de Nuevo León UANL (México). Professor of genetics in the Biological Sciences Faculty and researcher in the Immunology and Virology Laboratory of the UANL where investigates strategies for improve targeted gene and drug delivery systems to the lungs to treat to eliminate carcinogenic cells without affect healthy tissues using a system based in magnetic nanoparticles and chitosan.

Abstract

In the latest years, investigators have been treated to achieve more functional therapies and targeted to a specific organ without affect normal tissues or cells; the efficacy of non-viral gene delivery for therapies critically depends on a local concentration of plasmid DNA in the desired tissue and overcoming some barriers including rapid degradation by intra- and extracellular endonucleases. For this purpose magnetic carriers have been used which are commonly based on polymers since they have a variety of functional groups which can be used for specific applications. These polymers, whether natural or synthetic, have been used in the preparation of these carriers for years. In 1995 Mumpher et al., were the first to propose the use of chitosan as a DNA carrier. Chitosan-based nanoparticles are formed according to a 'bottom-up' approach as a result of self-association or cross-linking processes whereby the polymer chains are sorted into nanoscopic structures either by intra-molecular interactions. In these nanoparticles the drug can be entrapped or bound to the solid polymeric matrix.

In vivo, magnetic fields are focused below the site that is required to promote transfection and also to deliver the therapeutic gene to a specific organ or site within the body (Kavaz et al., 2008). 
Ideal anti-cancer therapies are those that can selectively destroy malignant cells without affecting healthy cells. There are currently agents that are specific in cancer cells in terms of efficacy and induction of cell death. TRAIL is an example of the molecule that selectively destroys malignant cells but not normal cells.

Previously we demonstrated that nanocarriers based in magnetic nanoparticles and directed by an external magnetic field are capable of being directed, retained and express a gene at the lungs. Nanoparticles with TRAIL gene and chitosan were constructed based in the ionic gelation method and were characterized by microscopy, zeta potential and retention analysis. Then transfected into mouse melanoma cells B16F10 and in lungs of mice with melanoma in the lungs as a strategy to inhibit the development of the melanoma in the lungs. We could demonstrate that our nanosystem can induce apoptosis both in vitro and in vivo by different techniques, although these results did not correlate with survival. Magnetic nanoparticles with chitosan and TRAIL are an efficient system to cause apoptosis in melanoma lung cells. More experimental information is needed to identify the rate-limiting steps in the apoptosis pathways that might be inhibited by new drugs and the consequences of such inhibition in lung repair, in addition to injury.

Audience will learn:
The audience will know a strategy that we used in our laboratory about targeted delivery system for genes based in magnetic nanoparticles, chitosan and a plasmid with a promoter that is activated by external magnetic field and how this allows to investigate new strategies of controlling the spatio-temporal expression of specific tissue genes. 

Also this provides the basis for raising that the nanocarrier system based in chitosan and plasmids with elements of response to magnetic field can have a great application in the therapeutics gene expression in a specific tissue for different diseases, in this case lung metastases. 

This as gene therapy can have a great social and economic impact in the area of health worldwide since it would avoid the use of conventional therapies which require various administrations and affect healthy organs and tissues causing very toxic side effects in addition to being very expensive.