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Magnetofection-based novel gene delivery system in salivary glands
타액선에서의 다공성 실리카 자성나노입자를 사용한 유전자 전달 방법의 개발

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Authors
이상우
Advisor
박경표, 이성중
Major
치의학대학원 치의학과
Issue Date
2015-02
Publisher
서울대학교 대학원
Keywords
Magnetofectiongene deliverysalivary glandiron oxide silica nanoparticleAquaporin-5
Description
학위논문 (석사)-- 서울대학교 대학원 : 치의학과, 2015. 2. 박경표, 이성중.
Abstract
Recently salivary glands are becoming a promising candidate for gene delivery to treat systemic and oral disease due to the several advantages. Salivary glands are multiple, well-encapsulated organ and thus risk of systemic side effects caused by the gene transfection is lower than other critical organs such as pancreas, kidney, or liver. In addition, since the gene delivery through duct cannulation is possible, non-invasive delivery, one of the gold standards in this field of study, can be achieved. In spite of those advantages there are several technical drawbacks in delivering genes to the salivary glands. Transfection efficiency and safety of conventional vectors has always been controversial issue. In case of viral vector inflammation and possibility of unexpected mutation are major problems. In contrast, non-viral vectors show little concern about those safety issues and biocompatibility but transfection efficiency is extremely lower than that of viral vectors. With the labyrinth-like complex anatomical structure of salivary glands and outward current of salivary flow, localization and uniform distribution of vector are even more hampered.
In this study, we report a magnetic gene transfer system combining extra-dermal magnetic field and Iron oxide-Mesoporous sillica-PEI nanoparticle to overcome those major hurdles of gene transfer to salivary glands. Uniformly constructed iron oxide nanoparticles were encapsulated by mesoporous silica, then electrostatically interacted with linear 10kDa PEI(Poly-ethyl-imine)(MSNNP in short). Characterization of synthesized MSNNP showed adequate zeta potential and excellent solution dispersion and magnetic responsiveness. MSNNPs were complexed with Aquaporin 5-GFP plasmids in 20:1(w/w) ratio then transferred to Human Salivary Gland(HSG) cell-line.
Under non-flowing condition transfection efficiency of MSNNP combined with magnetic field was 3 times higher than that of Lipofectamine 2000. Confocal image of HSG transfected with MSNNP showed distinctive AQP5-GFP protein expressed and located at membrane region. Magnetofection using MSNNP seems to be a practicable and promising system for non-viral gene delivery to salivary glands.
Language
English
URI
https://hdl.handle.net/10371/130798
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Theses (Master's Degree_치의학과)
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