{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79838"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79838","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Engineered Antibody Fragments Targeting Chemokine Receptors to Modulate Macrophage Phenotype for Tumor Inhibition","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Deci, Michael; 0000-0003-1249-6616"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Nguyen, Juliane","Pharmaceutical Sciences"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-07-29T19:36:27Z","date_published":"2019-07-29T19:36:27Z","updated_at":"2026-07-27T19:05:19Z","subjects":["pharmaceutical sciences"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/79838","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Nguyen, Juliane","Pharmaceutical Sciences"]},{"key":"dc:creator","label":"Author","values":["Deci, Michael; 0000-0003-1249-6616"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-07-29T19:36:27Z","2019","2019-05-16 11:12:22"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["pharmaceutical sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/79838"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","In Chapter I we give a perspective and comprehensive review on design principles of targeted nanocarriers with an emphasis on improving clinical translation. We discuss membrane fluidity and spatial control of ligand display, patterning of receptors, and importantly, how clustering of receptors can serve to amplify downstream signaling events. The review also notes that while spatiotemporal changes in receptor expression upon external cues and disease progression is reported, these changes are often disregarded and not considered in the design of nanocarriers. In many instances, targeted nanocarriers are engineered assuming a ‘static’ target, even though it is clear that throughout the progression of many diseases that this is not the case. Since conception, the relationship between targeted nanocarriers and receptors has been oversimplified. To achieve robust engagement of a ligand with its target, a better understanding of factors controlling receptor engagement is of utmost importance. Membrane fluidity, multivalency, and spatial control are highlighted as points of manipulation for designing nanocarriers that effectively treat disease. Expanding our knowledge and understanding how modulation of these parameters can better equip nanocarriers with spatiotemporal responsiveness and enhanced biological activity will be essential to make targeted nanomedicine a clinical reality. In Chapter II, we explore a protein scaffold for spatially controlled multiple protein display. Controlled organization of protein ligands can be used to improve selectivity of targeted therapeutics. As proof-of-concept, clathrin triskelions were investigated as a protein scaffold for multiple protein display using molecular epitope recognition. Binding of proteins to specific epitopes on clathrin is achieved via specific clathrin binding peptides (CBP). Further, the pharmacokinetics (PK) of the proteins are improved when attached to clathrin triskelions. This could have important applications for protein therapeutics with unfavorable PK, or those in which dual targeting of multiple receptors provides the greatest therapeutic effect. Controlled multiple protein display with a protein scaffold could have potential applications in vaccine development where an organized pattern of ligands could be more efficient at activation and recognition by antigen-presenting cells. Multiple protein display also could improve selectivity of targeted therapeutics to diseased tissues by targeting two or more receptors."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Engineered Antibody Fragments Targeting Chemokine Receptors to Modulate Macrophage Phenotype for Tumor Inhibition"]}]}],"canonical_facts":{"dc:contributor":["Nguyen, Juliane","Pharmaceutical Sciences"],"dc:creator":["Deci, Michael; 0000-0003-1249-6616"],"dc:date":["2019-07-29T19:36:27Z","2019","2019-05-16 11:12:22"],"dc:description":["Ph.D.","In Chapter I we give a perspective and comprehensive review on design principles of targeted nanocarriers with an emphasis on improving clinical translation. We discuss membrane fluidity and spatial control of ligand display, patterning of receptors, and importantly, how clustering of receptors can serve to amplify downstream signaling events. The review also notes that while spatiotemporal changes in receptor expression upon external cues and disease progression is reported, these changes are often disregarded and not considered in the design of nanocarriers. In many instances, targeted nanocarriers are engineered assuming a ‘static’ target, even though it is clear that throughout the progression of many diseases that this is not the case. Since conception, the relationship between targeted nanocarriers and receptors has been oversimplified. To achieve robust engagement of a ligand with its target, a better understanding of factors controlling receptor engagement is of utmost importance. Membrane fluidity, multivalency, and spatial control are highlighted as points of manipulation for designing nanocarriers that effectively treat disease. Expanding our knowledge and understanding how modulation of these parameters can better equip nanocarriers with spatiotemporal responsiveness and enhanced biological activity will be essential to make targeted nanomedicine a clinical reality. In Chapter II, we explore a protein scaffold for spatially controlled multiple protein display. Controlled organization of protein ligands can be used to improve selectivity of targeted therapeutics. As proof-of-concept, clathrin triskelions were investigated as a protein scaffold for multiple protein display using molecular epitope recognition. Binding of proteins to specific epitopes on clathrin is achieved via specific clathrin binding peptides (CBP). Further, the pharmacokinetics (PK) of the proteins are improved when attached to clathrin triskelions. This could have important applications for protein therapeutics with unfavorable PK, or those in which dual targeting of multiple receptors provides the greatest therapeutic effect. Controlled multiple protein display with a protein scaffold could have potential applications in vaccine development where an organized pattern of ligands could be more efficient at activation and recognition by antigen-presenting cells. Multiple protein display also could improve selectivity of targeted therapeutics to diseased tissues by targeting two or more receptors."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79838"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["pharmaceutical sciences"],"dc:title":["Engineered Antibody Fragments Targeting Chemokine Receptors to Modulate Macrophage Phenotype for Tumor Inhibition"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:19Z"}