Nanoparticles for biomedical applications

Q Science (General)

Child, Hannah ; Berry, Catherine

University:University of Glasgow

Department:Institute of Molecular Cell and Systems Biology

关键词: Nanoparticles;   

Others  :  http://theses.gla.ac.uk/3583/1/2012childphd.pdf

来源: University of Glasgow

【 摘 要 】

Modern day medicine is on the brink of a new age of therapy, which aims toharness the natural power of molecular biology for disease treatment. Thistherapy could include replacement of dysfunctional genes that cause disorderssuch as cystic fibrosis (Lommatzsch and Aris, 2009), or silencing the overexpressionof genes that cause disorders such as cancer (Pelengaris and Khan,2003). In both examples, the treatment of these genetic diseases lies in thedelivery of synthetic nucleic acids into diseased cells, the former being calledgene replacement therapy (Dobson, 2006a), and the latter being called RNAinterference (RNAi) therapy (Whitehead et al., 2009). While these techniqueshave long been in use as genetic research tools for gene transfection or silencingin vitro, their translation for use in clinical disease treatment has yet to beachieved. The main problem facing the development of these novel therapies isthe specific delivery of nucleic acids into diseased cells within the body. It ishoped that nanoparticles (NPs) can be used to overcome this problem, by actingas vehicles to transport nucleic acids through the body for specific delivery intodiseased cells. This feat can be aided by the attachment of additional functionalmolecules such as cell penetrating peptides (CPPs), targeting peptides,additional drug types and molecules for imaging during treatment. Manydifferent NP design strategies are currently under development. It is essentialfor new designs to be extensively tested for toxicity and efficiency in humancells before they can be successfully released into the clinic.As part of this effort, this PhD project has investigated two different NP designstrategies for drug delivery: 1) the use of a magnetic field (MF) and a CPP toincrease the delivery of iron oxide magnetic NPs (mNPs) to cells grown in tissueequivalent3D collagen gels, and 2) gold NPs (AuNPs) for the delivery of siRNA tosilence the c-myc oncogene for cancer treatment. In the first investigation, a MFand the CPP penetratin were found to increase mNP delivery to cells grown in3D. In the second investigation, AuNPs were assessed in a range of different celltypes (grown in 2D) for their performance in 4 main areas; cellular toxicity,cellular uptake, c-myc knockdown and effect on the cell cycle.