The overall objective of the proposed study is to develop and validate an in vitro multicellular layer (MCL) model that can be used to gain a better understanding of transport mechanisms and to facilitate testing a large number of experimental parameters that are pertinent to in vivo applications of electric field-mediated gene delivery. As a technique, electric field-mediated gene delivery is likely to be far from optimal since DNA transport in tumors is a complicated process. It is unpractical to optimize the technique using tumor tissues nor can it be optimized by using polymeric gels because of the absence of cells in gels. Therefore, I propose to develop and validate the MCL model (Specific Aim 1) since it is less expensive than tumor tissues and more relevant than polymeric gels. Using this model, I will identify effective pulse sequences forDNA transport (Specific Aim 1) and investigate effects of extracellular matrix (ECM) and cells on DNA mobility (Specific Aim 2). In addition, I will investigate the impact of DNA electrophoresis on transfection efficiency in electric field-mediated gene transfer (Specific Aim 3). Results from this study may lead to the identification of the most effective procedures for electric field-mediated gene transfer in solid tumors.
| Elliott, Nelita T; Yuan, Fan (2012) A microfluidic system for investigation of extravascular transport and cellular uptake of drugs in tumors. Biotechnol Bioeng 109:1326-35 |
| Elliott, Nelita; Lee, Tae; You, Lingchong et al. (2011) Proliferation behavior of E. coli in a three-dimensional in vitro tumor model. Integr Biol (Camb) 3:696-705 |
| Elliott, Nelita T; Yuan, Fan (2011) A review of three-dimensional in vitro tissue models for drug discovery and transport studies. J Pharm Sci 100:59-74 |
