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

TUNABLE IMMUNOSTIMULATORY NANOCARRIER FOR IMPROVING CANCER IMMUNOCHEMOTHERAPY

WAN, ZHUOYA (2017) TUNABLE IMMUNOSTIMULATORY NANOCARRIER FOR IMPROVING CANCER IMMUNOCHEMOTHERAPY. Master's Thesis, University of Pittsburgh. (Unpublished)

[img]
Preview
PDF
Download (2MB) | Preview

Abstract

Chemotherapy is the mainstream method of cancer therapy. In addition to direct cytotoxic effects on tumor cells, chemotherapy can induce antitumor immunity. The shortcomings of traditional chemotherapy are attributed to low solubility in aqueous solutions, rapid elimination, and lack of selectivity. In addition, cancers rapidly establish an immunological tolerance to the chemotherapy-induced antitumor immunity. The immune tolerance and suppression represent a major barrier to successful cancer treatment and are potential target for new therapeutics. Recent evidence demonstrates that an important mechanism underlying the immunological tolerance is the upregulated indoleamine-2,3-dioxygenase (IDO) expression in tumor cells or tumor-associated immune cells. Therefore, IDO pathway inhibition offers a potential for enhanced anti-tumor responses of chemotherapeutic agents.
In our previous study, systemic delivery of paclitaxel (PTX) using the PEG2k-Fmoc-NLG nanocarrier, a PEG-modified prodrug of NLG919 (an IDO1 selective inhibitor), led to a significantly enhanced anti-tumor effect of PTX by reactivating immunogenic responses. In this study we examined the therapeutic potential of a new nanocarrier that is based on a prodrug of 1-methyl-d-trptophan (1-D-MT). 1-D-MT is also an IDO inhibitor but has been reported to enhance antitumor immunity via different mechanism. The nanocarrier will be developed via reversible addition fragmentation transfer (RAFT) polymerization. In addition to the simplicity of the synthesis of the nanocarrier, the amount of 1-D-MT that can be incorporated into the polymer can be readily tuned via controlling the degree of polymerization.
Two 1-D-MT-based monomers were first synthesized followed by RAFT polymerization to give well-defined di-block co-polymers. Several polymers were synthesized and they varied in the molar ratio of hydrophilic POEG block/hydrophobic 1-D-MT block and the type of linker. Preliminary data showed that a 1-D-MT polymer with ethylene glycol vinyl ether linker can only load limited amounts of PTX and doxorubicin (DOX). Introduction of a vinylbenzyl chloride linker led to an improvement in drug loading capacity. More studies on the biophysical and biological properties of the new carrier are currently underway.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
WAN, ZHUOYAZHW64@PITT.EDUzhw64
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberLi, Jiangjil35@pitt.edujil35
Committee ChairLi, Songsol4@pitt.edusol4
Committee MemberYang, Dadyang@pitt.edu
Date: 29 August 2017
Date Type: Publication
Defense Date: 3 August 2017
Approval Date: 29 August 2017
Submission Date: 21 August 2017
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 47
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,Synergistic Effects,Immunochemotherapy, Breast Cancer Treatment
Date Deposited: 29 Aug 2017 12:17
Last Modified: 29 Aug 2018 05:15
URI: http://d-scholarship.pitt.edu/id/eprint/33072

Metrics

Monthly Views for the past 3 years

Plum Analytics


Actions (login required)

View Item View Item