Defense Date

2017

Document Type

Thesis

Degree Name

Master of Science

Department

Biomedical Engineering

Abstract

The immobilization of surface-modified polyamidoamine (PAMAM) dendrimers on the cell surface introduces a novel approach for efficient and specific cellular uptake of therapeutic-carrying nanoparticles. This cell surface-nanoparticle hybridization event takes place via bioorthogonal copper-free click chemistry between a dibenzocyclooctyne (DBCO) group on the dendrimer surface and azide-capped glycans expressed on the cell membrane through metabolic incorporation of azido sugars. This particular cell-nanoparticle hybridization method can be exploited to deliver a variety of therapeutic, genetic or fluorescent payloads directly into cells. Here, this method was employed to deliver plasmid DNA, siRNA and the hydrophobic anticancer drug Camptothecin (CPT) to enhance transfection and therapeutic efficacy. Native, acetylated, and PEGylated generation 4 (G4) PAMAM dendrimers were conjugated with DBCO. When introduced to azide expressing NIH3T3 fibroblasts and HN12 cancer cells, successful surface hybridization was achieved. The physiochemical properties of PAMAM dendrimers allowed for successful hydrophobic drug encapsulation and electrostatic nucleic acid condensation.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-5-2017

Available for download on Thursday, August 04, 2022

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