Publication Date

2012-08-30

Availability

Embargoed

Embargo Period

2014-08-30

Degree Name

Master of Science (MS)

Department

Biochemistry and Molecular Biology (Medicine)

Date of Defense

2012-07-13

First Committee Member

Sapna Deo

Second Committee Member

Sylvia Daunert

Third Committee Member

Zafar Nawaz

Abstract

Early detection of diseased cells can greatly alter the course of a disease process and create a better outcome for the patient. Lymphangioleiomyomatosis (LAM) is a disease characterized by gradual destruction of lung tissue caused by infiltration and proliferation of smooth muscle-like cells. Currently little can be done to treat the disease other than to ease symptoms. Early LAM diagnosis can greatly impact the course of the disease and the patient’s quality of life. In this work a sensitive imaging platform composed of a ligand targeted poly(amido)amine (PAMAM) nanocarrier complexed with Renilla luciferase (RLuc) is developed to target the lung epithelium. A molecule of RLuc was decorated externally with generation 5 PAMAM dendrimers covalently conjugated to three lung-targeting peptides to create a lung binding particle (LBP). In vitro studies with RLuc/LBP complexes and adenocarcinomic human alveolar basal epithelial cells (A549) cells showed that LBP targets A549 lung cells at a greater extent than a randomized peptide sequence conjugated PAMAM dendrimer. Mice injected with RLuc/LBP complexes and imaged using an in vivo imaging system (IVIS) were found to exhibit the highest bioluminescence signal in lung tissue consistently versus other organs. The results from the studies conducted in this work point to the potential use of the RLuc/LBP complexes for in vivo detection of lung epithelial cells.

Keywords

Bioluminescence; Targeting; Imaging; Nanoparticle

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