Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

An HA-based targeting system for improved lung cancer treatment

Li, Shichen (2024) An HA-based targeting system for improved lung cancer treatment. Master's Thesis, University of Pittsburgh. (Unpublished)

Download (657kB) | Preview


Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Platinum-based chemotherapy, such as cisplatin (CDDP), is a front-line treatment. However, the efficacy of platinum-related therapy is limited by the rapid development of drug resistance. Autophagy has been recognized as a critical factor in chemoresistance to CDDP. To overcome this, we introduced chloroquine (CQ) into the treatment, which is an effective autophagy inhibitor that can sensitize cancer cells to radiation and other anticancer drugs. To effectively co-deliver these two drugs, we developed a 5-aminosalicylic acid (5-ASA) derivatized nanocarrier based on hyaluronic acid (HA-ASA), which can actively target various types of cancer by targeting the overexpressed cell surface glycoprotein CD44.
We introduced 5-aminosalicylic acid (5-ASA) to the polymer (HA-ASA) as the hydrophobic core to form micelles. This novel nanocarrier can self-assemble in aqueous solution to form particles of ~100nm in size. Both CDDP and CQ can be loaded effectively into the HA-ASA micelles through various carrier/drug interactions with a final size of ~140 nm.
We showed that CDDP can induce autophagy in 3LL, FVBW17, and A549 cell lines and that the CDDP-CQ combination has a synergistic effect in vitro, with a combination index of smaller than 1. Meanwhile, we found that both CDDP and CQ can induce the expression of COX2, which can promote tumor progression, metastasis, and immunotherapy resistance. 5-ASA is an inhibitor of cyclooxygenase (COX), which can counteract the activity of the induced COX2.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLi,
Committee MemberZhang,
Committee MemberMa,
Date: 25 April 2024
Date Type: Publication
Defense Date: 28 March 2024
Approval Date: 25 April 2024
Submission Date: 23 April 2024
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 22
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: Non-small cell lung cancer; Nanoparticle; Drug delivery
Date Deposited: 25 Apr 2024 16:07
Last Modified: 25 Apr 2024 16:07


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item