Folic acid-modified methotrexate-conjugated gold nanoparticles as nano-sized trojans for drug delivery to folate receptor-positive cancer cells
Methotrexate (MTX), an analog of folic acid (FA), is a drug widely used in cancer treatment. To prevent its potential toxicity and enhance therapeutic efficacy, targeted drug delivery systems, especially nanotechnology-folate platforms, are a central strategy. Gold nanoparticles (AuNPs) are promisin...
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| Veröffentlicht in: | Nanotechnology 2020-08, Vol.31 (35), p.355101 |
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| creator | Yücel, O uz engelen, Asl han Emik, Serkan Önay-Uçar, Evren Arda, Nazl Gürda, Gülten |
| description | Methotrexate (MTX), an analog of folic acid (FA), is a drug widely used in cancer treatment. To prevent its potential toxicity and enhance therapeutic efficacy, targeted drug delivery systems, especially nanotechnology-folate platforms, are a central strategy. Gold nanoparticles (AuNPs) are promising candidates to be used as drug delivery systems because of their small particle sizes and their inertness for the body. In this study, glutathione (GSH)-coated FA-modified spherical AuNPs (5.6 nm) were successfully synthesized, and the anticancer activity of novel MTX-loaded (MTX/Au-GSH-FA) NPs (11 nm) was examined. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results showed that MTX/AuNPs possess spherical morphology, nanoscaled particle size, narrow size distribution, and good stability. In vitro studies showed that cytotoxicity of MTX/Au-GSH-FA to folate receptor-positive (FR+) human brain (U-87 MG) and cervical (HeLa) cancer cells enhanced significantly (∼3 and ∼10 fold, respectively) compared to free MTX while there was no significant effect in FR−negative human cell lines A549 (lung carcinoma), PC3 (prostate carcinoma), HEK-293 (healthy embryonic kidney). Moreover, the receptor specificity of the conjugate was shown by fluorescent microscopic imaging. In conclusion, these results indicate that the synthesized novel MTX/Au-GSH-FA NP complex seems to be a good candidate for effective and targeted delivery in FR+ cancer therapy. |
| doi_str_mv | 10.1088/1361-6528/ab9395 |
| format | Article |
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To prevent its potential toxicity and enhance therapeutic efficacy, targeted drug delivery systems, especially nanotechnology-folate platforms, are a central strategy. Gold nanoparticles (AuNPs) are promising candidates to be used as drug delivery systems because of their small particle sizes and their inertness for the body. In this study, glutathione (GSH)-coated FA-modified spherical AuNPs (5.6 nm) were successfully synthesized, and the anticancer activity of novel MTX-loaded (MTX/Au-GSH-FA) NPs (11 nm) was examined. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results showed that MTX/AuNPs possess spherical morphology, nanoscaled particle size, narrow size distribution, and good stability. In vitro studies showed that cytotoxicity of MTX/Au-GSH-FA to folate receptor-positive (FR+) human brain (U-87 MG) and cervical (HeLa) cancer cells enhanced significantly (∼3 and ∼10 fold, respectively) compared to free MTX while there was no significant effect in FR−negative human cell lines A549 (lung carcinoma), PC3 (prostate carcinoma), HEK-293 (healthy embryonic kidney). Moreover, the receptor specificity of the conjugate was shown by fluorescent microscopic imaging. In conclusion, these results indicate that the synthesized novel MTX/Au-GSH-FA NP complex seems to be a good candidate for effective and targeted delivery in FR+ cancer therapy.</description><identifier>ISSN: 0957-4484</identifier><identifier>EISSN: 1361-6528</identifier><identifier>DOI: 10.1088/1361-6528/ab9395</identifier><identifier>PMID: 32413875</identifier><identifier>CODEN: NNOTER</identifier><language>eng</language><publisher>England: IOP Publishing</publisher><subject>A549 Cells ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; cancer therapy ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Drug Synergism ; folate receptor ; Folic Acid - chemistry ; Folic Acid - pharmacology ; Glutathione - chemistry ; Gold - chemistry ; gold nanoparticles ; HEK293 Cells ; HeLa Cells ; Humans ; Metal Nanoparticles ; methotrexate ; Methotrexate - chemistry ; Methotrexate - pharmacology ; Particle Size ; PC-3 Cells ; targeted drug delivery</subject><ispartof>Nanotechnology, 2020-08, Vol.31 (35), p.355101</ispartof><rights>2020 IOP Publishing Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c370t-d5adccae9ea081f050e2f793f43b7248ac841b90608cdb5fe40a075b7eae5e493</citedby><cites>FETCH-LOGICAL-c370t-d5adccae9ea081f050e2f793f43b7248ac841b90608cdb5fe40a075b7eae5e493</cites><orcidid>0000-0001-7350-7767 ; 0000-0002-6005-9704 ; 0000-0003-2512-319X ; 0000-0002-1043-5652 ; 0000-0003-1389-2899 ; 0000-0003-1152-4881</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://iopscience.iop.org/article/10.1088/1361-6528/ab9395/pdf$$EPDF$$P50$$Giop$$H</linktopdf><link.rule.ids>314,776,780,27901,27902,53821,53868</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32413875$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yücel, O uz</creatorcontrib><creatorcontrib>engelen, Asl han</creatorcontrib><creatorcontrib>Emik, Serkan</creatorcontrib><creatorcontrib>Önay-Uçar, Evren</creatorcontrib><creatorcontrib>Arda, Nazl</creatorcontrib><creatorcontrib>Gürda, Gülten</creatorcontrib><title>Folic acid-modified methotrexate-conjugated gold nanoparticles as nano-sized trojans for drug delivery to folate receptor-positive cancer cells</title><title>Nanotechnology</title><addtitle>Nano</addtitle><addtitle>Nanotechnology</addtitle><description>Methotrexate (MTX), an analog of folic acid (FA), is a drug widely used in cancer treatment. To prevent its potential toxicity and enhance therapeutic efficacy, targeted drug delivery systems, especially nanotechnology-folate platforms, are a central strategy. Gold nanoparticles (AuNPs) are promising candidates to be used as drug delivery systems because of their small particle sizes and their inertness for the body. In this study, glutathione (GSH)-coated FA-modified spherical AuNPs (5.6 nm) were successfully synthesized, and the anticancer activity of novel MTX-loaded (MTX/Au-GSH-FA) NPs (11 nm) was examined. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results showed that MTX/AuNPs possess spherical morphology, nanoscaled particle size, narrow size distribution, and good stability. In vitro studies showed that cytotoxicity of MTX/Au-GSH-FA to folate receptor-positive (FR+) human brain (U-87 MG) and cervical (HeLa) cancer cells enhanced significantly (∼3 and ∼10 fold, respectively) compared to free MTX while there was no significant effect in FR−negative human cell lines A549 (lung carcinoma), PC3 (prostate carcinoma), HEK-293 (healthy embryonic kidney). Moreover, the receptor specificity of the conjugate was shown by fluorescent microscopic imaging. In conclusion, these results indicate that the synthesized novel MTX/Au-GSH-FA NP complex seems to be a good candidate for effective and targeted delivery in FR+ cancer therapy.</description><subject>A549 Cells</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>cancer therapy</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Drug Synergism</subject><subject>folate receptor</subject><subject>Folic Acid - chemistry</subject><subject>Folic Acid - pharmacology</subject><subject>Glutathione - chemistry</subject><subject>Gold - chemistry</subject><subject>gold nanoparticles</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Metal Nanoparticles</subject><subject>methotrexate</subject><subject>Methotrexate - chemistry</subject><subject>Methotrexate - pharmacology</subject><subject>Particle Size</subject><subject>PC-3 Cells</subject><subject>targeted drug delivery</subject><issn>0957-4484</issn><issn>1361-6528</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kFFrHCEUhSW0JNtt3vNUfC3ERkfdcR7LkqSBhb60z-LodeMyOw7qliR_on85TjbNUyhc8HI858D9ELpg9BujSl0xvmJkJRt1ZfqOd_IELd6kD2hBO9kSIZQ4Q59y3lHKmGrYKTrjjWBctXKB_t7EIVhsbHBkH13wARzeQ7mPJcGDKUBsHHeHbd0c3sbB4dGMcTKpBDtAxia_CCSHp2ooKe7MmLGPCbt02GIHQ_gD6RGXWMWhtuAEFqYSE5liDqX-YmtGCwlbGIb8GX30Zshw_vou0e-b61_rH2Tz8_Zu_X1DLG9pIU4aZ62BDgxVzFNJofFtx73gfdsIZawSrO_oiirreulBUENb2bdgQILo-BLRY69NMecEXk8p7E161Izqma2eQeoZpD6yrZEvx8h06Pfg3gL_YFbD5dEQ4qR38ZDGesH_-r6-Y59pas40l3Uko0xPzvNnsZqU4g</recordid><startdate>20200828</startdate><enddate>20200828</enddate><creator>Yücel, O uz</creator><creator>engelen, Asl han</creator><creator>Emik, Serkan</creator><creator>Önay-Uçar, Evren</creator><creator>Arda, Nazl</creator><creator>Gürda, Gülten</creator><general>IOP Publishing</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><orcidid>https://orcid.org/0000-0001-7350-7767</orcidid><orcidid>https://orcid.org/0000-0002-6005-9704</orcidid><orcidid>https://orcid.org/0000-0003-2512-319X</orcidid><orcidid>https://orcid.org/0000-0002-1043-5652</orcidid><orcidid>https://orcid.org/0000-0003-1389-2899</orcidid><orcidid>https://orcid.org/0000-0003-1152-4881</orcidid></search><sort><creationdate>20200828</creationdate><title>Folic acid-modified methotrexate-conjugated gold nanoparticles as nano-sized trojans for drug delivery to folate receptor-positive cancer cells</title><author>Yücel, O uz ; engelen, Asl han ; Emik, Serkan ; Önay-Uçar, Evren ; Arda, Nazl ; Gürda, Gülten</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c370t-d5adccae9ea081f050e2f793f43b7248ac841b90608cdb5fe40a075b7eae5e493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>A549 Cells</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>cancer therapy</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Drug Synergism</topic><topic>folate receptor</topic><topic>Folic Acid - chemistry</topic><topic>Folic Acid - pharmacology</topic><topic>Glutathione - chemistry</topic><topic>Gold - chemistry</topic><topic>gold nanoparticles</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Metal Nanoparticles</topic><topic>methotrexate</topic><topic>Methotrexate - chemistry</topic><topic>Methotrexate - pharmacology</topic><topic>Particle Size</topic><topic>PC-3 Cells</topic><topic>targeted drug delivery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yücel, O uz</creatorcontrib><creatorcontrib>engelen, Asl han</creatorcontrib><creatorcontrib>Emik, Serkan</creatorcontrib><creatorcontrib>Önay-Uçar, Evren</creatorcontrib><creatorcontrib>Arda, Nazl</creatorcontrib><creatorcontrib>Gürda, Gülten</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Nanotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yücel, O uz</au><au>engelen, Asl han</au><au>Emik, Serkan</au><au>Önay-Uçar, Evren</au><au>Arda, Nazl</au><au>Gürda, Gülten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Folic acid-modified methotrexate-conjugated gold nanoparticles as nano-sized trojans for drug delivery to folate receptor-positive cancer cells</atitle><jtitle>Nanotechnology</jtitle><stitle>Nano</stitle><addtitle>Nanotechnology</addtitle><date>2020-08-28</date><risdate>2020</risdate><volume>31</volume><issue>35</issue><spage>355101</spage><pages>355101-</pages><issn>0957-4484</issn><eissn>1361-6528</eissn><coden>NNOTER</coden><abstract>Methotrexate (MTX), an analog of folic acid (FA), is a drug widely used in cancer treatment. To prevent its potential toxicity and enhance therapeutic efficacy, targeted drug delivery systems, especially nanotechnology-folate platforms, are a central strategy. Gold nanoparticles (AuNPs) are promising candidates to be used as drug delivery systems because of their small particle sizes and their inertness for the body. In this study, glutathione (GSH)-coated FA-modified spherical AuNPs (5.6 nm) were successfully synthesized, and the anticancer activity of novel MTX-loaded (MTX/Au-GSH-FA) NPs (11 nm) was examined. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results showed that MTX/AuNPs possess spherical morphology, nanoscaled particle size, narrow size distribution, and good stability. In vitro studies showed that cytotoxicity of MTX/Au-GSH-FA to folate receptor-positive (FR+) human brain (U-87 MG) and cervical (HeLa) cancer cells enhanced significantly (∼3 and ∼10 fold, respectively) compared to free MTX while there was no significant effect in FR−negative human cell lines A549 (lung carcinoma), PC3 (prostate carcinoma), HEK-293 (healthy embryonic kidney). Moreover, the receptor specificity of the conjugate was shown by fluorescent microscopic imaging. In conclusion, these results indicate that the synthesized novel MTX/Au-GSH-FA NP complex seems to be a good candidate for effective and targeted delivery in FR+ cancer therapy.</abstract><cop>England</cop><pub>IOP Publishing</pub><pmid>32413875</pmid><doi>10.1088/1361-6528/ab9395</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-7350-7767</orcidid><orcidid>https://orcid.org/0000-0002-6005-9704</orcidid><orcidid>https://orcid.org/0000-0003-2512-319X</orcidid><orcidid>https://orcid.org/0000-0002-1043-5652</orcidid><orcidid>https://orcid.org/0000-0003-1389-2899</orcidid><orcidid>https://orcid.org/0000-0003-1152-4881</orcidid></addata></record> |
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| ispartof | Nanotechnology, 2020-08, Vol.31 (35), p.355101 |
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| subjects | A549 Cells Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology cancer therapy Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Drug Synergism folate receptor Folic Acid - chemistry Folic Acid - pharmacology Glutathione - chemistry Gold - chemistry gold nanoparticles HEK293 Cells HeLa Cells Humans Metal Nanoparticles methotrexate Methotrexate - chemistry Methotrexate - pharmacology Particle Size PC-3 Cells targeted drug delivery |
| title | Folic acid-modified methotrexate-conjugated gold nanoparticles as nano-sized trojans for drug delivery to folate receptor-positive cancer cells |
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