{"id":{"repo_id":"ohiolink","oai_identifier":"oai:etd.ohiolink.edu:case1364833269"},"canonical_url":"https://search.dev.ndltd.org/etd/ohiolink/oai:etd.ohiolink.edu:case1364833269","repository":{"repo_id":"ohiolink","name":"OhioLINK","base_url":"https://etd.ohiolink.edu/acprod/odb_etd/ws/oai/oai"},"display":{"title":"EGFR-Targeted Polymeric Micelles For Targeted Pc 4-PDT Of Oropharyngeal Tumors","abstract":"Photodynamic Therapy (PDT) holds great promise for the treatment of head and neck (H&N) carcinomas where repeated loco-regional therapy often becomes necessary due to the highly aggressive and recurrent nature of the cancers. Conventional surgery, chemotherapy and radiotherapy approaches cause significant cosmetic and functional damage to H&N tissue if repeated, whereas, PDT can allow a safe repeatable treatment alternative. While interstitial light delivery technologies are being refined for PDT of H&N and other cancers, a parallel clinically relevant research area is the formulation of photosensitizers in nanovehicles that allow systemic administration yet preferential enhanced uptake in the tumor. This approach can render dual-selectivity of PDT, by harnessing both the drug and the light delivery within the tumor. The broad long-term research objective is to develop an effective nanomedicine platform for targeted delivery of the photosensitizer drug Pc 4 to sites of head and neck cancer to enhance the clinical repertoire of Pc 4-induced photodynamic therapy (PDT) in these malignancies. The specific aims are to: (1) Determine encapsulation and release kinetics of Pc 4 in biocompatible block-copolymer micelles, (2) Modify micelle surface with EGFR-specific ligands and investigate cancer cell targeting of the surface-modified micelles in vitro, and, (3) Investigate targeted PDT effects on SCC cell lines in vitro and suitable animal models in vivo with Pc 4- loaded EGFR-targeted micelle formulations. Using fluorescence spectroscopy and confocal microscopy, it has been demonstrated in vitro that the EGFR-targeted Pc 4-nanoformulation undergoes faster and higher uptake in EGFR-overexpressing H&N cells. It is further demonstrated that this enhanced Pc 4 uptake results in significant cell-killing and drastically reduced post-PDT clonogenicity. Building on this in vitro data, it is shown that the EGFR-targeted Pc 4-nanoformulation results in enhanced intratumoral drug uptake and subsequent enhanced PDT response, in vivo, in SCC-15 xenografts in mice. Altogether our results show significant promise towards establishing a cell-targeted photodynamic nanomedicine for effective treatment of H&N carcinomas.","abstract_html":"Photodynamic Therapy (PDT) holds great promise for the treatment of head and neck (H&N) carcinomas where repeated loco-regional therapy often becomes necessary due to the highly aggressive and recurrent nature of the cancers. Conventional surgery, chemotherapy and radiotherapy approaches cause significant cosmetic and functional damage to H&N tissue if repeated, whereas, PDT can allow a safe repeatable treatment alternative. While interstitial light delivery technologies are being refined for PDT of H&N and other cancers, a parallel clinically relevant research area is the formulation of photosensitizers in nanovehicles that allow systemic administration yet preferential enhanced uptake in the tumor. This approach can render dual-selectivity of PDT, by harnessing both the drug and the light delivery within the tumor. The broad long-term research objective is to develop an effective nanomedicine platform for targeted delivery of the photosensitizer drug Pc 4 to sites of head and neck cancer to enhance the clinical repertoire of Pc 4-induced photodynamic therapy (PDT) in these malignancies. The specific aims are to: (1) Determine encapsulation and release kinetics of Pc 4 in biocompatible block-copolymer micelles, (2) Modify micelle surface with EGFR-specific ligands and investigate cancer cell targeting of the surface-modified micelles in vitro, and, (3) Investigate targeted PDT effects on SCC cell lines in vitro and suitable animal models in vivo with Pc 4- loaded EGFR-targeted micelle formulations. Using fluorescence spectroscopy and confocal microscopy, it has been demonstrated in vitro that the EGFR-targeted Pc 4-nanoformulation undergoes faster and higher uptake in EGFR-overexpressing H&N cells. It is further demonstrated that this enhanced Pc 4 uptake results in significant cell-killing and drastically reduced post-PDT clonogenicity. Building on this in vitro data, it is shown that the EGFR-targeted Pc 4-nanoformulation results in enhanced intratumoral drug uptake and subsequent enhanced PDT response, in vivo, in SCC-15 xenografts in mice. Altogether our results show significant promise towards establishing a cell-targeted photodynamic nanomedicine for effective treatment of H&N carcinomas.","abstract_has_math":false,"creators":["Master, Alyssa M."],"institution":"Case Western Reserve University School of Graduate Studies","degree_name":"Doctor of Philosophy","degree_level":"doctoral","degree_discipline":"Biomedical Engineering","degree_department":null,"school":null,"contributors":["Sen Gupta, Anirban","Marchant, Roger"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-08-23","date_published":"2013-08-23","updated_at":"2026-07-24T03:37:16Z","subjects":["Biomedical Engineering","nanoparticles","photodynamic therapy","targeted drug delivery"],"languages":["English"],"rights":["unrestricted","This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. 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It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://rave.ohiolink.edu/etdc/view?acc_num=case1364833269"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Photodynamic Therapy (PDT) holds great promise for the treatment of head and neck (H&N) carcinomas where repeated loco-regional therapy often becomes necessary due to the highly aggressive and recurrent nature of the cancers. Conventional surgery, chemotherapy and radiotherapy approaches cause significant cosmetic and functional damage to H&N tissue if repeated, whereas, PDT can allow a safe repeatable treatment alternative. While interstitial light delivery technologies are being refined for PDT of H&N and other cancers, a parallel clinically relevant research area is the formulation of photosensitizers in nanovehicles that allow systemic administration yet preferential enhanced uptake in the tumor. This approach can render dual-selectivity of PDT, by harnessing both the drug and the light delivery within the tumor. The broad long-term research objective is to develop an effective nanomedicine platform for targeted delivery of the photosensitizer drug Pc 4 to sites of head and neck cancer to enhance the clinical repertoire of Pc 4-induced photodynamic therapy (PDT) in these malignancies. The specific aims are to: (1) Determine encapsulation and release kinetics of Pc 4 in biocompatible block-copolymer micelles, (2) Modify micelle surface with EGFR-specific ligands and investigate cancer cell targeting of the surface-modified micelles in vitro, and, (3) Investigate targeted PDT effects on SCC cell lines in vitro and suitable animal models in vivo with Pc 4- loaded EGFR-targeted micelle formulations. Using fluorescence spectroscopy and confocal microscopy, it has been demonstrated in vitro that the EGFR-targeted Pc 4-nanoformulation undergoes faster and higher uptake in EGFR-overexpressing H&N cells. It is further demonstrated that this enhanced Pc 4 uptake results in significant cell-killing and drastically reduced post-PDT clonogenicity. Building on this in vitro data, it is shown that the EGFR-targeted Pc 4-nanoformulation results in enhanced intratumoral drug uptake and subsequent enhanced PDT response, in vivo, in SCC-15 xenografts in mice. Altogether our results show significant promise towards establishing a cell-targeted photodynamic nanomedicine for effective treatment of H&N carcinomas."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf","p.313","5.74 MB"]},{"key":"dc:title","label":"Title","values":["EGFR-Targeted Polymeric Micelles For Targeted Pc 4-PDT Of Oropharyngeal Tumors"]}]}],"canonical_facts":{"dc:contributor":["Sen Gupta, Anirban","Marchant, Roger"],"dc:creator":["Master, Alyssa M."],"dc:date":["2013-08-23"],"dc:description":["Photodynamic Therapy (PDT) holds great promise for the treatment of head and neck (H&N) carcinomas where repeated loco-regional therapy often becomes necessary due to the highly aggressive and recurrent nature of the cancers. Conventional surgery, chemotherapy and radiotherapy approaches cause significant cosmetic and functional damage to H&N tissue if repeated, whereas, PDT can allow a safe repeatable treatment alternative. While interstitial light delivery technologies are being refined for PDT of H&N and other cancers, a parallel clinically relevant research area is the formulation of photosensitizers in nanovehicles that allow systemic administration yet preferential enhanced uptake in the tumor. This approach can render dual-selectivity of PDT, by harnessing both the drug and the light delivery within the tumor. The broad long-term research objective is to develop an effective nanomedicine platform for targeted delivery of the photosensitizer drug Pc 4 to sites of head and neck cancer to enhance the clinical repertoire of Pc 4-induced photodynamic therapy (PDT) in these malignancies. The specific aims are to: (1) Determine encapsulation and release kinetics of Pc 4 in biocompatible block-copolymer micelles, (2) Modify micelle surface with EGFR-specific ligands and investigate cancer cell targeting of the surface-modified micelles in vitro, and, (3) Investigate targeted PDT effects on SCC cell lines in vitro and suitable animal models in vivo with Pc 4- loaded EGFR-targeted micelle formulations. Using fluorescence spectroscopy and confocal microscopy, it has been demonstrated in vitro that the EGFR-targeted Pc 4-nanoformulation undergoes faster and higher uptake in EGFR-overexpressing H&N cells. It is further demonstrated that this enhanced Pc 4 uptake results in significant cell-killing and drastically reduced post-PDT clonogenicity. Building on this in vitro data, it is shown that the EGFR-targeted Pc 4-nanoformulation results in enhanced intratumoral drug uptake and subsequent enhanced PDT response, in vivo, in SCC-15 xenografts in mice. Altogether our results show significant promise towards establishing a cell-targeted photodynamic nanomedicine for effective treatment of H&N carcinomas."],"dc:format":["application/pdf","p.313","5.74 MB"],"dc:identifier":["http://rave.ohiolink.edu/etdc/view?acc_num=case1364833269"],"dc:language":["English"],"dc:publisher":["Case Western Reserve University School of Graduate Studies / OhioLINK"],"dc:rights":["unrestricted","This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. 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