PPI Dendronized Gold Nanoparticles for Drug Delivery Applications- Synthesis, Characterization and Biological Evaluation
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Date
2018-01-01
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Department
Chemistry & Biochemistry
Program
Chemistry
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Access limited to the UMBC community. Item may possibly be obtained via Interlibrary Loan thorugh a local library, pending author/copyright holder's permission.
This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
Abstract
One of the promising avenues for delivery of poorly water soluble chemotherapeutics specifically to tumors and in increased effective concentration is through the use of nanoparticles. Presently various novel nanoparticle-based drug delivery systems (liposomes, dendrimers, gold nanoparticles) are being investigated. The use of nanovectors offers several compelling advantages such as their inherent versatility, increased multivalency and ability to passively target tumors through the enhanced permeability and retention (EPR) effect. Within the diverse field of nanovectors, dendrons and dendrimers (synthetic macromolecular polymers with tightly controlled geometry and structure) have shown impressive potential for targeted delivery of therapeutics. This project is aimed towards the preparation of dendron-capped gold nanovectors (hydrodynamic radius 30 nm) with various terminal functional groups (amine, carboxylate) for their use in drug delivery and in vivo imaging. The aforementioned nanovectors have been designed with four complimentary components: (i) A 20 nm gold core; (ii) Dendrons carrying imaging agents such as: (DOTA chelated Gd) for MRI and water-soluble Cy 7 dye for fluorescence imaging; (iii) Dendrons carrying tumor recognition moieties (e.g. monoclonal antibodies) for active targeting; and (iv) Dendrons with functional groups that facilitate effective drug conjugation. In the current research, gold nanoparticles have been utilized as a non-classical dendrimer core due to its well-established biocompatibility. The dimension of the gold nanoparticles has been carefully selected to minimize rapid clearance via renal filtration or elimination via macrophages due to opsonization. For this project, poly(propyleneimine) PPI dendrons were prepared with various terminal functionalities. Additionally, a TEG (Tetra Ethylene Glycol) spacer was incorporated at the focal point of the dendron to minimize steric hindrance between the dendrons on the gold core as well as to increase biocompatibility of the nano-construct. The cytotoxicity and cellular fate of the thus prepared dendronized gold nanoparticles was studied in MCF-7 breast cancer cell lines using fluorescence microscopy. Furthermore, the integrity of the cellular membrane was studied as a function of the surface charge of nanoparticle coatings