Targeting Serpin B9 via Gemcitabine-based siRNA/drug Dual-Nanocarrier for Improved Pancreatic Cancer Therapy

Mu, Yiqing (2024) Targeting Serpin B9 via Gemcitabine-based siRNA/drug Dual-Nanocarrier for Improved Pancreatic Cancer Therapy. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Granzyme B is a potent cytotoxic molecule produced by cytotoxic T cells and NK cells to kill cancer cells. Serpinb9 is an endogenous inhibitor of granzyme B and is co-expressed in cytotoxic T cells to protect themselves from self-inflicted damage. Interestingly, many types of cancer cells also co-express serpinb9 and granzyme B. In this study, we showed that serpinb9 expression is correlated with gemcitabine resistance in pancreatic cancer. Based on this finding, we proposed to develop a novel therapeutic approach that combines gemcitabine chemotherapy with siRNA-mediated serpinb9 knockdown. We have developed a gemcitabine prodrug nanoparticle system capable of co-delivery of gemcitabine and siSBP9. Our nanoparticles are small in size and close to neutral in surface charge. These nanoparticles were highly effective in tumor-targeting in tumor-bearing mice. Moreover, our combined therapy showed significantly enhanced anti-tumor effect and improved tumor immune microenvironment.

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Details

Item Type:	University of Pittsburgh ETD
Status:	Unpublished
Creators/Authors:	Creators Email Pitt Username ORCID Mu, Yiqing yim45@pitt.edu yim45
ETD Committee:	Title Member Email Address Pitt Username ORCID Committee Chair Li, Song sol4@pitt.edu sol4 Committee Member Zhang, Wei weizhang@pitt.edu weizhang Committee Member Patel, Sravan Kumar srp75@pitt.edu srp75 Thesis Advisor Li, Song sol4@pitt.edu sol4
Date:	30 April 2024
Date Type:	Publication
Defense Date:	29 March 2024
Approval Date:	30 April 2024
Submission Date:	17 April 2024
Access Restriction:	2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages:	35
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:	nano medicine, siRNA delivery, combination therapy
Date Deposited:	30 Apr 2024 15:18
Last Modified:	30 Apr 2024 15:18
URI:	http://d-scholarship.pitt.edu/id/eprint/46151

Available Versions of this Item

• Targeting Serpin B9 via Gemcitabine-based siRNA/drug Dual-Nanocarrier for Improved Pancreatic Cancer Therapy. (deposited UNSPECIFIED)
  • Targeting Serpin B9 via Gemcitabine-based siRNA/drug Dual-Nanocarrier for Improved Pancreatic Cancer Therapy. (deposited 30 Apr 2024 15:18) [Currently Displayed]

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