Date of Award

2017

Document Type

Thesis

Degree Name

Master of Science (M.S.)

Department

Pharmaceutical and Chemical Sciences

First Advisor

Xin Guo

First Committee Member

Xiaoling Li

Second Committee Member

John C. Livesey

Abstract

Proteins are large biomolecules that have great therapeutic potential in treating many human diseases. However, chemical/enzymatic degradation, denaturation, and poor penetration into cells are some of the challenges for clinical use of intracellular proteins.

Previously, our group has developed cationic lipid-coated magnesium phosphate nanoparticle (LP MgP NP-CAT) formulations to enhance the intracellular delivery of the negatively charged protein catalase. The goal of the current research is to develop a formulation to deliver cytochrome c (CytC), a positively charged protein into lung cancer cells A549. Specifically, this thesis research prepares and tests liposome-coated magnesium phosphate nanoparticle for delivery of cytochrome c (CytC LP/MgP).

CytC LP/MgP was designed, prepared and characterized, showing that it had an average diameter around 150 nm and ζ-potential around +30 mV. The morphology of CytC LP/MgP was validated by transmission electron microscopy.

CytC LP/MgP successfully led to the attachment of CytC to A549 cells, as supported by fluorescence imaging. Intracellular delivery of CytC alleviated the cytotoxicity of cationic lipids in A549 cells, as suggested by the MTS assay on cell viability, which could facilitate the clinical use of cationic lipids in drug delivery systems.

Share

COinS