{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/105110"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/105110","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Trigger-responsive nanomedicines through controlled chemistry","abstract":"The aim of my Ph.D. thesis is to develop trigger-responsive prodrug platform to address the nanoparticle (NP) formulation issue in cancer therapeutics. By designing a trigger-responsive camptothecin (CPT) prodrug structure, it was demonstrated for the first time that a small molecule prodrug could be encapsulated in PEGylated nanoparticles with quantitative drug loading efficiency and more than 50% drug loading. The nanoparticles were shown to have controlled release profile in response to cancer-specific trigger. A series of dimeric CPT derivatives were designed that are responsive to various in vivo applicable triggers to study the formulation mechanism. The prodrug library suggested that the dimeric prodrug structure and the flexible trigger-responsive side chain are both critical to the high drug loading formulation. A hypoxia-responsive CPT dimeric prodrug was further developed and was co-encapsulated with photodynamic sensitizer, chlorin e6, in one NP for combination therapy to combat tumor resistance to photodynamic therapy (PDT) caused by a hypoxic environment. The ultra-high drug loading nanoparticles with controllable release and defined nano-structure mark a milestone in the formulation of nanomedicine and will have significant impact on nanomedicine platform design as well as their clinical translation. In connection with the dimeric prodrug design, a trigger-responsive amphiphilic polymeric nano-assembly is also explored for cancer treatment based on thiol-responsive chain-shattering polymeric therapeutics. The polymeric therapeutics showed controlled self-assembly behavior and good in vivo anti-tumor efficacy. To develop novel polymeric biomaterials for biomedical application, I also studied dynamic aromatic hindered urea chemistry as degradable polymeric materials. The aromatic hindered ureas have hundred times higher dynamic exchange kinetics (k-1) than the reported aliphatic hindered ureas and showed fast hydrolytic degradation in polymers with pH-independent kinetics. The room temperature self-healing property of the aromatic hindered ureas in a cross-linked gel was explored as a proof of concept as a potent self-healable biomaterials.","abstract_html":"The aim of my Ph.D. thesis is to develop trigger-responsive prodrug platform to address the nanoparticle (NP) formulation issue in cancer therapeutics. By designing a trigger-responsive camptothecin (CPT) prodrug structure, it was demonstrated for the first time that a small molecule prodrug could be encapsulated in PEGylated nanoparticles with quantitative drug loading efficiency and more than 50% drug loading. The nanoparticles were shown to have controlled release profile in response to cancer-specific trigger. A series of dimeric CPT derivatives were designed that are responsive to various in vivo applicable triggers to study the formulation mechanism. The prodrug library suggested that the dimeric prodrug structure and the flexible trigger-responsive side chain are both critical to the high drug loading formulation. A hypoxia-responsive CPT dimeric prodrug was further developed and was co-encapsulated with photodynamic sensitizer, chlorin e6, in one NP for combination therapy to combat tumor resistance to photodynamic therapy (PDT) caused by a hypoxic environment. The ultra-high drug loading nanoparticles with controllable release and defined nano-structure mark a milestone in the formulation of nanomedicine and will have significant impact on nanomedicine platform design as well as their clinical translation. In connection with the dimeric prodrug design, a trigger-responsive amphiphilic polymeric nano-assembly is also explored for cancer treatment based on thiol-responsive chain-shattering polymeric therapeutics. The polymeric therapeutics showed controlled self-assembly behavior and good in vivo anti-tumor efficacy. To develop novel polymeric biomaterials for biomedical application, I also studied dynamic aromatic hindered urea chemistry as degradable polymeric materials. The aromatic hindered ureas have hundred times higher dynamic exchange kinetics (k-1) than the reported aliphatic hindered ureas and showed fast hydrolytic degradation in polymers with pH-independent kinetics. The room temperature self-healing property of the aromatic hindered ureas in a cross-linked gel was explored as a proof of concept as a potent self-healable biomaterials.","abstract_has_math":false,"creators":["Cai, Kaimin"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Materials Science & Engr","degree_department":null,"school":null,"contributors":["Lu, Yi","Cheng, Jianjun","Ferguson, Andrew L.","Kilian, Kristopher A.","Leal, Cecilia"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-08-23T20:44:15Z","date_published":"2019-08-23T20:44:15Z","updated_at":"2026-07-22T22:24:44Z","subjects":["Trigger-responsive materials","Nanomedicine","photodynamic therapy","hindered urea bond","dynamic chemistry"],"languages":["en"],"rights":["Copyright 2017 Kaimin Cai"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/105110","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Lu, Yi","Cheng, Jianjun","Ferguson, Andrew L.","Kilian, Kristopher A.","Leal, Cecilia"]},{"key":"dc:creator","label":"Author","values":["Cai, Kaimin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-08-23T20:44:15Z","2021-08-24T09:15:16Z","2017-06-15","2017-08"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Materials Science & Engr"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Trigger-responsive materials","Nanomedicine","photodynamic therapy","hindered urea bond","dynamic chemistry"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2017 Kaimin Cai"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/105110"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The aim of my Ph.D. thesis is to develop trigger-responsive prodrug platform to address the nanoparticle (NP) formulation issue in cancer therapeutics. By designing a trigger-responsive camptothecin (CPT) prodrug structure, it was demonstrated for the first time that a small molecule prodrug could be encapsulated in PEGylated nanoparticles with quantitative drug loading efficiency and more than 50% drug loading. The nanoparticles were shown to have controlled release profile in response to cancer-specific trigger. A series of dimeric CPT derivatives were designed that are responsive to various in vivo applicable triggers to study the formulation mechanism. The prodrug library suggested that the dimeric prodrug structure and the flexible trigger-responsive side chain are both critical to the high drug loading formulation. A hypoxia-responsive CPT dimeric prodrug was further developed and was co-encapsulated with photodynamic sensitizer, chlorin e6, in one NP for combination therapy to combat tumor resistance to photodynamic therapy (PDT) caused by a hypoxic environment. The ultra-high drug loading nanoparticles with controllable release and defined nano-structure mark a milestone in the formulation of nanomedicine and will have significant impact on nanomedicine platform design as well as their clinical translation. In connection with the dimeric prodrug design, a trigger-responsive amphiphilic polymeric nano-assembly is also explored for cancer treatment based on thiol-responsive chain-shattering polymeric therapeutics. The polymeric therapeutics showed controlled self-assembly behavior and good in vivo anti-tumor efficacy. To develop novel polymeric biomaterials for biomedical application, I also studied dynamic aromatic hindered urea chemistry as degradable polymeric materials. The aromatic hindered ureas have hundred times higher dynamic exchange kinetics (k-1) than the reported aliphatic hindered ureas and showed fast hydrolytic degradation in polymers with pH-independent kinetics. The room temperature self-healing property of the aromatic hindered ureas in a cross-linked gel was explored as a proof of concept as a potent self-healable biomaterials.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-08-01","The student, Kaimin Cai, accepted the attached license on 2017-05-18 at 12:49.","The student, Kaimin Cai, submitted this Dissertation for approval on 2017-05-18 at 12:57.","This Dissertation was approved for publication on 2017-06-15 at 09:06.","DSpace SAF Submission Ingestion Package generated from Vireo submission #11165 on 2019-08-22 at 16:17:28","Made available in DSpace on 2019-08-23T20:44:15Z (GMT). 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By designing a trigger-responsive camptothecin (CPT) prodrug structure, it was demonstrated for the first time that a small molecule prodrug could be encapsulated in PEGylated nanoparticles with quantitative drug loading efficiency and more than 50% drug loading. The nanoparticles were shown to have controlled release profile in response to cancer-specific trigger. A series of dimeric CPT derivatives were designed that are responsive to various in vivo applicable triggers to study the formulation mechanism. The prodrug library suggested that the dimeric prodrug structure and the flexible trigger-responsive side chain are both critical to the high drug loading formulation. A hypoxia-responsive CPT dimeric prodrug was further developed and was co-encapsulated with photodynamic sensitizer, chlorin e6, in one NP for combination therapy to combat tumor resistance to photodynamic therapy (PDT) caused by a hypoxic environment. The ultra-high drug loading nanoparticles with controllable release and defined nano-structure mark a milestone in the formulation of nanomedicine and will have significant impact on nanomedicine platform design as well as their clinical translation. In connection with the dimeric prodrug design, a trigger-responsive amphiphilic polymeric nano-assembly is also explored for cancer treatment based on thiol-responsive chain-shattering polymeric therapeutics. The polymeric therapeutics showed controlled self-assembly behavior and good in vivo anti-tumor efficacy. To develop novel polymeric biomaterials for biomedical application, I also studied dynamic aromatic hindered urea chemistry as degradable polymeric materials. The aromatic hindered ureas have hundred times higher dynamic exchange kinetics (k-1) than the reported aliphatic hindered ureas and showed fast hydrolytic degradation in polymers with pH-independent kinetics. The room temperature self-healing property of the aromatic hindered ureas in a cross-linked gel was explored as a proof of concept as a potent self-healable biomaterials.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-08-01","The student, Kaimin Cai, accepted the attached license on 2017-05-18 at 12:49.","The student, Kaimin Cai, submitted this Dissertation for approval on 2017-05-18 at 12:57.","This Dissertation was approved for publication on 2017-06-15 at 09:06.","DSpace SAF Submission Ingestion Package generated from Vireo submission #11165 on 2019-08-22 at 16:17:28","Made available in DSpace on 2019-08-23T20:44:15Z (GMT). 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