{"id":{"repo_id":"mississippi","oai_identifier":"oai:egrove.olemiss.edu:etd-2338"},"canonical_url":"https://search.dev.ndltd.org/etd/mississippi/oai:egrove.olemiss.edu:etd-2338","repository":{"repo_id":"mississippi","name":"University of Mississippi","base_url":"https://egrove.olemiss.edu/do/oai/"},"display":{"title":"Synthesis and Characterization of Redox-Sensitive Polymer and Prodrug for Targeted Drug Delivery","abstract":"Systemic administration of chemotherapeutics is associated with various side effects deriving from accumulation in off-target sites and acute toxicity of the drugs. In the past decade, engineering targeted drug delivery platforms arose as a novel paradigm to overcome such obstacles and ultimately achieve advanced forms of chemotherapy. This thesis reports successful syntheses of l-RSP, a redox-sensitive self-immolative polymer, and DNS-SN38, thiol-sensitive SN-38 prodrug, as potential candidates for targeted drug delivery platforms. By covalently conjugating a redox-trigger (p-nitrobenzyl alcohol) and self-immolative linker (p-hydroxybenzyl alcohol) to the cyclization spacer (n-2-(hydroxyethyl)ethylene diamine), a novel self-immolative monomer was obtained. Polymerization of the respective monomer yielded a linear redox-sensitive polymer (l-RSP) that is capable of systemic degradation via sequential 1,6-elimination and 1,5-cyclization reactions upon redox-stimulus. Ultimately, the polymer’s potential for biomedical application was simulated through in vitro redox-triggered release of paclitaxel from polymeric nanoparticles. SN-38 (7-ethyl-10-hydroxy-camptothecin), a potent metabolite of irinotecan (CPT-11), has been extensively investigated in the past for direct usage in order to fully exploit its cytotoxic potency. Here, 2,4-dinitrobenzene sulfonyl (DNS) moiety was conjugated to SN-38 to furnish a thiol-sensitive prodrug, denoted as DNS-SN38, that can be activated in the intracellular regions with GSH abundance. Furthermore, due to strong electron-withdrawing potential of DNS, the inherent fluorescence of SN-38 could be virtually quenched with intact conjugation. By investigating the prodrug’s activation property upon thiol-sensitive trigger cleavage via fluorescence activation and cytotoxicity against A2780 and mCherry+OCSC1-F2 cell lines, its vast potential as a viable theranostic agent was demonstrated.","abstract_html":"Systemic administration of chemotherapeutics is associated with various side effects deriving from accumulation in off-target sites and acute toxicity of the drugs. In the past decade, engineering targeted drug delivery platforms arose as a novel paradigm to overcome such obstacles and ultimately achieve advanced forms of chemotherapy. This thesis reports successful syntheses of l-RSP, a redox-sensitive self-immolative polymer, and DNS-SN38, thiol-sensitive SN-38 prodrug, as potential candidates for targeted drug delivery platforms. By covalently conjugating a redox-trigger (p-nitrobenzyl alcohol) and self-immolative linker (p-hydroxybenzyl alcohol) to the cyclization spacer (n-2-(hydroxyethyl)ethylene diamine), a novel self-immolative monomer was obtained. Polymerization of the respective monomer yielded a linear redox-sensitive polymer (l-RSP) that is capable of systemic degradation via sequential 1,6-elimination and 1,5-cyclization reactions upon redox-stimulus. Ultimately, the polymer’s potential for biomedical application was simulated through in vitro redox-triggered release of paclitaxel from polymeric nanoparticles. SN-38 (7-ethyl-10-hydroxy-camptothecin), a potent metabolite of irinotecan (CPT-11), has been extensively investigated in the past for direct usage in order to fully exploit its cytotoxic potency. Here, 2,4-dinitrobenzene sulfonyl (DNS) moiety was conjugated to SN-38 to furnish a thiol-sensitive prodrug, denoted as DNS-SN38, that can be activated in the intracellular regions with GSH abundance. Furthermore, due to strong electron-withdrawing potential of DNS, the inherent fluorescence of SN-38 could be virtually quenched with intact conjugation. By investigating the prodrug’s activation property upon thiol-sensitive trigger cleavage via fluorescence activation and cytotoxicity against A2780 and mCherry+OCSC1-F2 cell lines, its vast potential as a viable theranostic agent was demonstrated.","abstract_has_math":false,"creators":["Whang, Chang-Hee"],"institution":null,"degree_name":"M.S. in Pharmaceutical Science","degree_level":"Thesis","degree_discipline":"Pharmaceutics and Drug Delivery","degree_department":null,"school":null,"contributors":["Seongbong Jo","Michael A. Repka","Chalet Tan"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-01-01T08:00:00Z","date_published":"2018-01-01T08:00:00Z","updated_at":"2026-07-24T03:06:44Z","subjects":["Drug delivery","Polymer","Prodrug","Redox","self immolative","sn 38","Pharmacy and Pharmaceutical Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://egrove.olemiss.edu/etd/1339","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Seongbong Jo","Michael A. 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In the past decade, engineering targeted drug delivery platforms arose as a novel paradigm to overcome such obstacles and ultimately achieve advanced forms of chemotherapy. This thesis reports successful syntheses of l-RSP, a redox-sensitive self-immolative polymer, and DNS-SN38, thiol-sensitive SN-38 prodrug, as potential candidates for targeted drug delivery platforms. By covalently conjugating a redox-trigger (p-nitrobenzyl alcohol) and self-immolative linker (p-hydroxybenzyl alcohol) to the cyclization spacer (n-2-(hydroxyethyl)ethylene diamine), a novel self-immolative monomer was obtained. Polymerization of the respective monomer yielded a linear redox-sensitive polymer (l-RSP) that is capable of systemic degradation via sequential 1,6-elimination and 1,5-cyclization reactions upon redox-stimulus. Ultimately, the polymer’s potential for biomedical application was simulated through in vitro redox-triggered release of paclitaxel from polymeric nanoparticles. SN-38 (7-ethyl-10-hydroxy-camptothecin), a potent metabolite of irinotecan (CPT-11), has been extensively investigated in the past for direct usage in order to fully exploit its cytotoxic potency. Here, 2,4-dinitrobenzene sulfonyl (DNS) moiety was conjugated to SN-38 to furnish a thiol-sensitive prodrug, denoted as DNS-SN38, that can be activated in the intracellular regions with GSH abundance. Furthermore, due to strong electron-withdrawing potential of DNS, the inherent fluorescence of SN-38 could be virtually quenched with intact conjugation. By investigating the prodrug’s activation property upon thiol-sensitive trigger cleavage via fluorescence activation and cytotoxicity against A2780 and mCherry+OCSC1-F2 cell lines, its vast potential as a viable theranostic agent was demonstrated."]},{"key":"dc:title","label":"Title","values":["Synthesis and Characterization of Redox-Sensitive Polymer and Prodrug for Targeted Drug Delivery"]}]}],"canonical_facts":{"dc:contributor":["Seongbong Jo","Michael A. Repka","Chalet Tan"],"dc:creator":["Whang, Chang-Hee"],"dc:date.available":["2020-01-23T08:00:00Z"],"dc:description.abstract":["Systemic administration of chemotherapeutics is associated with various side effects deriving from accumulation in off-target sites and acute toxicity of the drugs. In the past decade, engineering targeted drug delivery platforms arose as a novel paradigm to overcome such obstacles and ultimately achieve advanced forms of chemotherapy. This thesis reports successful syntheses of l-RSP, a redox-sensitive self-immolative polymer, and DNS-SN38, thiol-sensitive SN-38 prodrug, as potential candidates for targeted drug delivery platforms. By covalently conjugating a redox-trigger (p-nitrobenzyl alcohol) and self-immolative linker (p-hydroxybenzyl alcohol) to the cyclization spacer (n-2-(hydroxyethyl)ethylene diamine), a novel self-immolative monomer was obtained. Polymerization of the respective monomer yielded a linear redox-sensitive polymer (l-RSP) that is capable of systemic degradation via sequential 1,6-elimination and 1,5-cyclization reactions upon redox-stimulus. Ultimately, the polymer’s potential for biomedical application was simulated through in vitro redox-triggered release of paclitaxel from polymeric nanoparticles. SN-38 (7-ethyl-10-hydroxy-camptothecin), a potent metabolite of irinotecan (CPT-11), has been extensively investigated in the past for direct usage in order to fully exploit its cytotoxic potency. Here, 2,4-dinitrobenzene sulfonyl (DNS) moiety was conjugated to SN-38 to furnish a thiol-sensitive prodrug, denoted as DNS-SN38, that can be activated in the intracellular regions with GSH abundance. Furthermore, due to strong electron-withdrawing potential of DNS, the inherent fluorescence of SN-38 could be virtually quenched with intact conjugation. By investigating the prodrug’s activation property upon thiol-sensitive trigger cleavage via fluorescence activation and cytotoxicity against A2780 and mCherry+OCSC1-F2 cell lines, its vast potential as a viable theranostic agent was demonstrated."],"dc:identifier":["https://egrove.olemiss.edu/etd/1339"],"dc:subject":["Drug delivery","Polymer","Prodrug","Redox","self immolative","sn 38","Pharmacy and Pharmaceutical Sciences"],"dc:title":["Synthesis and Characterization of Redox-Sensitive Polymer and Prodrug for Targeted Drug Delivery"],"thesis:degree_discipline":["Pharmaceutics and Drug Delivery"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["M.S. in Pharmaceutical Science"]},"updated_at":"2026-07-24T03:06:44Z"}