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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 (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Mu, Yiqingyim45@pitt.eduyim45
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLi, Songsol4@pitt.edusol4
Committee MemberZhang, Weiweizhang@pitt.eduweizhang
Committee MemberPatel, Sravan Kumarsrp75@pitt.edusrp75
Thesis AdvisorLi, Songsol4@pitt.edusol4
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

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