Moharil, Pearl
(2019)
Folic acid conjugated polymer as a nano-carrier: dual targeting of tumor cells and tumor microenvironment.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Polymeric micelles have been extensively used in pharmaceutical research for drug delivery. However, most polymeric systems have sizes above 100 nm, which may limit effective extravasation into tumors that are poorly vascularized and have dense stroma. In this project, we synthesized a pVBSS backbone and conjugated it with Gemcitabine (GEM) via a disulfide bond. This system was then used to load Doxorubicin (DOX), for co-delivery of GEM and DOX to tumor cells. We hypothesize that the cellular uptake of pVBSS-GEM can be enhanced by conjugating a targeting ligand, such as folate (FA), to the polymer backbone. This could actively target the FR, which is overexpressed not only on several types of cancer cells but also on the tumor-associated M2 macrophages present in the microenvironment.
FA-pVBSS-GEM/DOX was successfully synthesized and it formed small spherical micelles of 10 nm diameter. The targeting micelle showed a sustained DOX release profile and successfully increased DOX uptake in 4T1.2 and KB cells in vitro. In vivo, systemic delivery of FA-pVBSS-GEM/DOX led to higher micellar accumulation in the tumor environment and remarkably reduced the tumor growth in a murine 4T1.2 breast cancer model.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
4 April 2019 |
| Date Type: |
Publication |
| Defense Date: |
29 March 2019 |
| Approval Date: |
4 April 2019 |
| Submission Date: |
4 April 2019 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Number of Pages: |
55 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Polymeric micelles, targeted drug delivery, tumor microenvironment |
| Date Deposited: |
04 Apr 2019 14:46 |
| Last Modified: |
04 Apr 2024 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/36289 |
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