Mechanistic investigation into selective cytotoxic activities of gold nanoparticles functionalized with epidermal growth factor variants
Epidermal growth factor (EGF) gains unique selective cytotoxicity against cancer cells upon conjugation with gold nanoparticles (GNPs). We have previously developed several lysine-free EGF mutants for favorable interactions between the nanoparticle conjugates with EGF receptor (EGFR) and found one m...
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| Veröffentlicht in: | Analytical sciences 2023-03, Vol.39 (3), p.395-405 |
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| creator | Zhang, Aiwen Abdellatef, Shimaa A. Nakanishi, Jun |
| description | Epidermal growth factor (EGF) gains unique selective cytotoxicity against cancer cells upon conjugation with gold nanoparticles (GNPs). We have previously developed several lysine-free EGF mutants for favorable interactions between the nanoparticle conjugates with EGF receptor (EGFR) and found one mutant (SR: K28S/K48R) showing stronger anticancer activities. However, the exact mechanisms for the selective cytotoxicity enhancement in the SR mutant remained unsolved. In this study, we analyzed how the nanoparticle conjugates of EGF variants interacted differently with A431 cancer cells, in terms of receptor binding, activation, and trafficking. Our results indicate that the essential feature of the SR-GNP conjugates in the cytotoxicity enhancement is their preferential activation of the clathrin-independent endocytosis pathway. It is suggested that we should focus on not only ligand-receptor binding affinity but also the selectivity of the receptor endocytic route to optimize the anticancer effects in this modality.
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| doi_str_mv | 10.1007/s44211-022-00256-7 |
| format | Article |
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Graphical abstract</description><subject>Analytical Chemistry</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Clathrin - metabolism</subject><subject>Endocytosis - physiology</subject><subject>Epidermal Growth Factor - metabolism</subject><subject>Gold</subject><subject>Metal Nanoparticles</subject><subject>Original Paper</subject><issn>0910-6340</issn><issn>1348-2246</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1uGyEUhVHUqnGcvEAWEctuJuV3mFlWUfMjJeqmXSOGuThEY3CAceI-QR67uE677Ao4nPtduAehc0ouKSHqSxaCUdoQxhpCmGwbdYQWlIuuYUy0H9CC9JQ0LRfkGJ3k_EQIZR1jn9Axb1veS9kv0NsD2EcTfC7eYh-2UDcrU3wM9VQizjCBLX4L2O5KLPG12sxe8MVDxtHhVZxGHEyIG5MqZKqqm4PdI8zkf8GIX3x5xLDxI6S1mfAqxZcquIqJCW9N8iaUfIo-OjNlOHtfl-jn9bcfV7fN_febu6uv942tjy4NU5xz1jknu7Gnou0HrqzojJODGEgrFMixY4MhI2XDYDn0rpOyE8pJZXvl-BJ9PnA3KT7P9bt67bOFaTIB4pw1U61UisraZ4nYwWpTzDmB05vk1ybtNCV6n4A-JKBrAvpPAlrVoot3_jysYfxX8nfk1cAPhlyvwgqSfopzqrPK_8P-BmlJlXQ</recordid><startdate>20230301</startdate><enddate>20230301</enddate><creator>Zhang, Aiwen</creator><creator>Abdellatef, Shimaa A.</creator><creator>Nakanishi, Jun</creator><general>Springer Nature Singapore</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4457-6581</orcidid></search><sort><creationdate>20230301</creationdate><title>Mechanistic investigation into selective cytotoxic activities of gold nanoparticles functionalized with epidermal growth factor variants</title><author>Zhang, Aiwen ; Abdellatef, Shimaa A. ; Nakanishi, Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c366t-2733328ff58d91469b37c48af5b4b0647e5d82ba0d12bbc3e9f855847f57c97f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analytical Chemistry</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Clathrin - metabolism</topic><topic>Endocytosis - physiology</topic><topic>Epidermal Growth Factor - metabolism</topic><topic>Gold</topic><topic>Metal Nanoparticles</topic><topic>Original Paper</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Aiwen</creatorcontrib><creatorcontrib>Abdellatef, Shimaa A.</creatorcontrib><creatorcontrib>Nakanishi, Jun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Analytical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Aiwen</au><au>Abdellatef, Shimaa A.</au><au>Nakanishi, Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanistic investigation into selective cytotoxic activities of gold nanoparticles functionalized with epidermal growth factor variants</atitle><jtitle>Analytical sciences</jtitle><stitle>ANAL. SCI</stitle><addtitle>Anal Sci</addtitle><date>2023-03-01</date><risdate>2023</risdate><volume>39</volume><issue>3</issue><spage>395</spage><epage>405</epage><pages>395-405</pages><issn>0910-6340</issn><eissn>1348-2246</eissn><abstract>Epidermal growth factor (EGF) gains unique selective cytotoxicity against cancer cells upon conjugation with gold nanoparticles (GNPs). We have previously developed several lysine-free EGF mutants for favorable interactions between the nanoparticle conjugates with EGF receptor (EGFR) and found one mutant (SR: K28S/K48R) showing stronger anticancer activities. However, the exact mechanisms for the selective cytotoxicity enhancement in the SR mutant remained unsolved. In this study, we analyzed how the nanoparticle conjugates of EGF variants interacted differently with A431 cancer cells, in terms of receptor binding, activation, and trafficking. Our results indicate that the essential feature of the SR-GNP conjugates in the cytotoxicity enhancement is their preferential activation of the clathrin-independent endocytosis pathway. It is suggested that we should focus on not only ligand-receptor binding affinity but also the selectivity of the receptor endocytic route to optimize the anticancer effects in this modality.
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| ispartof | Analytical sciences, 2023-03, Vol.39 (3), p.395-405 |
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| language | eng |
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| source | MEDLINE; Freely Accessible Japanese Titles; EZB-FREE-00999 freely available EZB journals; SpringerLink Journals - AutoHoldings |
| subjects | Analytical Chemistry Chemistry Chemistry and Materials Science Clathrin - metabolism Endocytosis - physiology Epidermal Growth Factor - metabolism Gold Metal Nanoparticles Original Paper |
| title | Mechanistic investigation into selective cytotoxic activities of gold nanoparticles functionalized with epidermal growth factor variants |
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