DOI
https://doi.org/10.25772/K8ZJ-CE57
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