{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/44777"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/44777","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Development of a click chemistry approach for cancer cell targeting and evaluating the effect of protein corona on active targeting yield","abstract":"The routine approach for targeting nanoparticle delivery vehicles to cancer cells is by incorporating targeting ligands (e.g. antibodies or aptamers) to the surface of nanoparticles (NPs). Although targeting ligands are known to interact with specific receptors in the membranes of cancer cells, resulting in enhanced NP uptake, these functionalized NPs have an undesirable biodistribution and unfavorable targeting efficacy. Here we demonstrate a novel approach to target NPs to the cancer cells via click chemistry. Cancer cells are first metabolically labeled with an azide-modified monosaccharide (azidosugar). In the second step, NPs that are functionalized with highly-reactive cycloalkynes selectively bind to the cancer cells due to a spontaneous click reaction between the cycloalkynes on NP’s surfaces and the metabolically incorporated azide groups in the cell membranes. Our results show that HeLa and Chinese hamster ovary (CHO) cells are successfully labeled with azidosugars, and cycloalkyne-functionalized silica NPs bind to the metabolically labeled cells via the click reaction. The click chemistry reaction was also used to study the effect of protein adsorption on active NP targeting. Upon exposure of NPs to the biological environment, proteins and other biomolecules bind to the NPs and cover their surfaces. This protein coating, which is called the protein corona, may reduce the targeting capability of functionalized NPs by screening their targeting ligands. Here we used cycloalkyne-functionalized silica NPs that can bind to the azide-modified silicon substrates to study this effect. The results demonstrate that the formation of protein corona significantly decreased the conjugation of functionalized NPs to the substrate.","abstract_html":"The routine approach for targeting nanoparticle delivery vehicles to cancer cells is by incorporating targeting ligands (e.g. antibodies or aptamers) to the surface of nanoparticles (NPs). Although targeting ligands are known to interact with specific receptors in the membranes of cancer cells, resulting in enhanced NP uptake, these functionalized NPs have an undesirable biodistribution and unfavorable targeting efficacy. Here we demonstrate a novel approach to target NPs to the cancer cells via click chemistry. Cancer cells are first metabolically labeled with an azide-modified monosaccharide (azidosugar). In the second step, NPs that are functionalized with highly-reactive cycloalkynes selectively bind to the cancer cells due to a spontaneous click reaction between the cycloalkynes on NP’s surfaces and the metabolically incorporated azide groups in the cell membranes. Our results show that HeLa and Chinese hamster ovary (CHO) cells are successfully labeled with azidosugars, and cycloalkyne-functionalized silica NPs bind to the metabolically labeled cells via the click reaction. The click chemistry reaction was also used to study the effect of protein adsorption on active NP targeting. Upon exposure of NPs to the biological environment, proteins and other biomolecules bind to the NPs and cover their surfaces. This protein coating, which is called the protein corona, may reduce the targeting capability of functionalized NPs by screening their targeting ligands. Here we used cycloalkyne-functionalized silica NPs that can bind to the azide-modified silicon substrates to study this effect. The results demonstrate that the formation of protein corona significantly decreased the conjugation of functionalized NPs to the substrate.","abstract_has_math":false,"creators":["Mirshafiee, Vahid"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"M.S.","degree_level":"Thesis","degree_discipline":"Chemical Engineering","degree_department":null,"school":null,"contributors":["Kraft, Mary L."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-05-28T19:19:29Z","date_published":"2013-05-28T19:19:29Z","updated_at":"2026-07-22T22:25:34Z","subjects":["Nanoparticle","Targeted Drug Delivery","Click Chemistry","Protein Corona"],"languages":["en"],"rights":["Copyright 2013 Vahid Mirshafiee"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/44777","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kraft, Mary L."]},{"key":"dc:creator","label":"Author","values":["Mirshafiee, Vahid"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013-05-28T19:19:29Z","2015-05-28T10:01:46Z","2013-05"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemical Engineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.S."]},{"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":["Nanoparticle","Targeted Drug Delivery","Click Chemistry","Protein Corona"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2013 Vahid Mirshafiee"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/44777"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The routine approach for targeting nanoparticle delivery vehicles to cancer cells is by incorporating targeting ligands (e.g. antibodies or aptamers) to the surface of nanoparticles (NPs). Although targeting ligands are known to interact with specific receptors in the membranes of cancer cells, resulting in enhanced NP uptake, these functionalized NPs have an undesirable biodistribution and unfavorable targeting efficacy. Here we demonstrate a novel approach to target NPs to the cancer cells via click chemistry. Cancer cells are first metabolically labeled with an azide-modified monosaccharide (azidosugar). In the second step, NPs that are functionalized with highly-reactive cycloalkynes selectively bind to the cancer cells due to a spontaneous click reaction between the cycloalkynes on NP’s surfaces and the metabolically incorporated azide groups in the cell membranes. Our results show that HeLa and Chinese hamster ovary (CHO) cells are successfully labeled with azidosugars, and cycloalkyne-functionalized silica NPs bind to the metabolically labeled cells via the click reaction. The click chemistry reaction was also used to study the effect of protein adsorption on active NP targeting. Upon exposure of NPs to the biological environment, proteins and other biomolecules bind to the NPs and cover their surfaces. This protein coating, which is called the protein corona, may reduce the targeting capability of functionalized NPs by screening their targeting ligands. Here we used cycloalkyne-functionalized silica NPs that can bind to the azide-modified silicon substrates to study this effect. The results demonstrate that the formation of protein corona significantly decreased the conjugation of functionalized NPs to the substrate.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2013-03-29T21:02:48Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Mirshafiee_Vahid.pdf: 2130171 bytes, checksum: da3c07e9f06db21e4f33906962936e1b (MD5)","Made available in DSpace on 2013-05-28T19:19:29Z (GMT). No. of bitstreams: 2 Vahid_Mirshafiee.pdf: 2130174 bytes, checksum: 836662bb400f2385cbeef63c32723452 (MD5) license.txt: 4066 bytes, checksum: fde631cbc6e0c962d6f4ef4f113dc8d3 (MD5)","Restriction data tranferred 2014-07-01T11:16:51-05:00 Original Data Group with Access Administrator Release Date: 2015-05-28 14:21:22 UTC Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system","Item marked as restricted to the 'Administrator' Group (id=1) by Seth Robbins (srobbins@illinois.edu) on 2013-05-28T19:21:44Z Item is restricted until 2015-05-28T19:21:22Z","Limited Restriction Lifted for Item 44752 on 2015-05-28T10:01:46Z."]},{"key":"dc:title","label":"Title","values":["Development of a click chemistry approach for cancer cell targeting and evaluating the effect of protein corona on active targeting yield"]}]}],"canonical_facts":{"dc:contributor":["Kraft, Mary L."],"dc:creator":["Mirshafiee, Vahid"],"dc:date":["2013-05-28T19:19:29Z","2015-05-28T10:01:46Z","2013-05"],"dc:description":["The routine approach for targeting nanoparticle delivery vehicles to cancer cells is by incorporating targeting ligands (e.g. antibodies or aptamers) to the surface of nanoparticles (NPs). Although targeting ligands are known to interact with specific receptors in the membranes of cancer cells, resulting in enhanced NP uptake, these functionalized NPs have an undesirable biodistribution and unfavorable targeting efficacy. Here we demonstrate a novel approach to target NPs to the cancer cells via click chemistry. Cancer cells are first metabolically labeled with an azide-modified monosaccharide (azidosugar). In the second step, NPs that are functionalized with highly-reactive cycloalkynes selectively bind to the cancer cells due to a spontaneous click reaction between the cycloalkynes on NP’s surfaces and the metabolically incorporated azide groups in the cell membranes. Our results show that HeLa and Chinese hamster ovary (CHO) cells are successfully labeled with azidosugars, and cycloalkyne-functionalized silica NPs bind to the metabolically labeled cells via the click reaction. The click chemistry reaction was also used to study the effect of protein adsorption on active NP targeting. Upon exposure of NPs to the biological environment, proteins and other biomolecules bind to the NPs and cover their surfaces. This protein coating, which is called the protein corona, may reduce the targeting capability of functionalized NPs by screening their targeting ligands. Here we used cycloalkyne-functionalized silica NPs that can bind to the azide-modified silicon substrates to study this effect. The results demonstrate that the formation of protein corona significantly decreased the conjugation of functionalized NPs to the substrate.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2013-03-29T21:02:48Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Mirshafiee_Vahid.pdf: 2130171 bytes, checksum: da3c07e9f06db21e4f33906962936e1b (MD5)","Made available in DSpace on 2013-05-28T19:19:29Z (GMT). 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