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Radhika Bhave - Thesis Final.pdf (3.08 MB)

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Nanoparticle-Cell Lipid Membrane Biophysical Interaction and its Role in Developing Tumor Targeted Nanoparticles

Bhave, Radhika
http://rave.ohiolink.edu/etdc/view?acc_num=csu1433170085

Abstract Details

2015, Master of Science in Biomedical Engineering, Cleveland State University, Washkewicz College of Engineering.
Tumor targeted nanoparticles could improve drug delivery of the encapsulated cancer therapeutics to the tumor while reducing their non-specific side effects. However, complex conjugation chemistry, weak antibody-nanoparticle binding, and finite number of receptors available for nanoparticle binding could limit the efficacy of tumor targeted nanoparticles. Therefore, there is need for a new approach to improve nanoparticle localization in tumors. Physical properties of nanoparticles particularly their surface properties have shown to influence in vitro cellular uptake, in vivo biodistribution and tumor localization of nanoparticles. Apart from physical characteristics of nanoparticles, their uptake has also been shown to depend on the cell type. Additionally, progression of disease such as cancer can cause changes in the cell membrane lipid composition, and thereby influence nanoparticle-cell membrane interactions and cellular uptake of nanoparticles. The research described in this thesis explores an interesting approach that explores the differences in the cell membrane lipid composition as well as modification in nanoparticle surface characteristics to design nanoparticles that would preferentially target tumors. In our study, biophysical interactions between nanoparticles and endothelial cell model membrane demonstrate the effect of surface chemistry of nanoparticles on such interactions. Nanoparticles with sulfate and amine surface chemistry show higher interactions with model membrane as compared to nanoparticles with carboxyl and amidine surface chemistry. Biophysical characteristics of cell membrane lipids extracted from normal endothelial and cancerous cells demonstrate the fluidic nature of cancerous cell membrane as compared to the rigid and condensed nature of normal endothelial cell membrane. Nanoparticle-cell membrane lipid interactions demonstrate more selective interactions between nanoparticles with sulfate surface chemistry and cancer cell membrane lipids than with normal cell membrane lipids. On the other hand, nanoparticles with amine surface chemistry demonstrate non-selective interactions with both cancerous and endothelial cell lipid membranes. Nanoparticles loaded with a hydrophobic near infrared dye were used to quantitatively determine biodistribution and tumor localization of nanoparticles in vivo, using an optical imaging technique. Surface chemistry of nanoparticles was shown to influence nanoparticles biodistribution and tumor localization. Nanoparticles with sulfate groups demonstrate higher tumor localization and retention as compared to nanoparticles with amine and carboxyl groups. The results demonstrate that selectivity of nanoparticle with sulfate surface chemistry towards cancerous cell lipid membrane translates in greater tumor localization in vivo. We further studied effect of surface of PLGA-based biodegradable nanoparticles and their interactions with model membranes. These biodegradable nanoparticles when formulated using emulsion-solvent evaporation method retains a fraction of emulsifier, polyvinyl alcohol (PVA) associated with the surface, commonly referred as residual PVA. In this study, nanoparticles were formulated with PVA of different molecular weight and degree of hydrolysis. Our findings illustrated that surface associated residual PVA significantly influences biophysical interactions of nanoparticles with endothelial cell model membrane. Biophysical interactions between nanoparticles and cell lipid membranes could potentially be explored to understand the effect of surface characteristics of nanoparticles on cellular uptake, biodistribution and targeting.
Vinod Labhasetwar, PhD (Committee Chair)
Nolan Holland, PhD (Committee Member)
Mekki Bayachou, PhD (Committee Member)
Kiril Streletzky, PhD (Committee Member)
Xue-Long Sun, PhD (Committee Member)
Maciej Zborowski, PhD (Committee Member)
Biomedical Engineering

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Citations

  • Bhave, R. (2015). Nanoparticle-Cell Lipid Membrane Biophysical Interaction and its Role in Developing Tumor Targeted Nanoparticles [Master's thesis, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1433170085

    APA Style (7th edition)

  • Bhave, Radhika. Nanoparticle-Cell Lipid Membrane Biophysical Interaction and its Role in Developing Tumor Targeted Nanoparticles . 2015. Cleveland State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1433170085.

    MLA Style (8th edition)

  • Bhave, Radhika. "Nanoparticle-Cell Lipid Membrane Biophysical Interaction and its Role in Developing Tumor Targeted Nanoparticles ." Master's thesis, Cleveland State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=csu1433170085

    Chicago Manual of Style (17th edition)

csu1433170085
478
© 2015, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.