Burkert, Seth
(2019)
Metal Nanoparticle-Decorated Carbon Nanocups for Drug Delivery.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Carbon nanotubes are viewed as an ideal vehicle for drug delivery due to their ease of chemical functionalization, proven ability to penetrate cell membranes, and tunable length scales which can affect bio-distribution. However, concerns as to the potential harmful side effects of carbon nanomaterials have been reported, halting their implementation for biological applications. The incorporation of nitrogen dopants into the graphitic lattice of carbon nanotubes results in sputtered growth yielding a bamboo or stacked cup nanotube structures. The cup structures are held together through weak van der Waals forces and as such can be separated into individual cups for potential drug delivery applications. Due to their unique electrical and structural properties, nanocups represent an exciting material for a wide range of applications. We first investigated the electrochemical response of synthesized nanocups towards the oxygen reduction reaction which has important implications in fuel cell technology. Stacked nanocups were then separated into individual and short stacked segments and effectively sealed through conjugation with gold nanoparticles resulting in a unique drug delivery vehicle. The method of separation was investigated to maximize the propensity for individual nanocups to be corked with gold nanoparticles. Furthermore, the metal decoration of nanocups was explored in response to changes in the local environment illustrating a robust synthetic procedure. The developed gold nanoparticle corked nanocups showed the ability to be loaded with target molecules and effectively degraded through biologically relevant enzymes releasing the loaded cargo. These enzymes are overexpressed in important target cells in the tumor microenvironment creating a built-in targeted delivery system for cancer therapies. The culmination of this report illustrates nanocups loaded with paclitaxel, a common chemotherapeutic agent, and systemically delivered to tumor-bearing mice resulting in tumor growth inhibition with 25–30% of mice being tumor free after 2–3 weeks. The results of this report demonstrate effective drug delivery design and a novel immunotherapy strategy dependent upon systemic cell delivery to affect change in the tumor microenvironment.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
20 June 2019 |
| Date Type: |
Publication |
| Defense Date: |
9 April 2019 |
| Approval Date: |
20 June 2019 |
| Submission Date: |
15 April 2019 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
163 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Carbon nanotubes, gold nanoparticles, drug delivery, enzyamtic degradation |
| Date Deposited: |
20 Jun 2019 14:26 |
| Last Modified: |
20 Jun 2020 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/36497 |
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