Targeted Delivery of DNA Topoisomerase Inhibitor SN38 to Intracranial Tumors of Glioblastoma Using Sub‐5 Ultrafine Iron Oxide Nanoparticles
Effectively delivering therapeutics for treating brain tumors is hindered by the physical and biological barriers in the brain. Even with the compromised blood–brain barrier and highly angiogenic blood–tumor barrier seen in glioblastoma (GBM), most drugs, including nanomaterial‐based formulations, h...
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| Veröffentlicht in: | Advanced healthcare materials 2022-07, Vol.11 (14), p.e2102816-n/a |
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| creator | Li, Yuancheng Xie, Manman Jones, Joshua B. Zhang, Zhaobin Wang, Zi Dang, Tu Wang, Xinyu Lipowska, Malgorzata Mao, Hui |
| description | Effectively delivering therapeutics for treating brain tumors is hindered by the physical and biological barriers in the brain. Even with the compromised blood–brain barrier and highly angiogenic blood–tumor barrier seen in glioblastoma (GBM), most drugs, including nanomaterial‐based formulations, hardly reach intracranial tumors. This work investigates sub‐5 nm ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier for delivering DNA topoisomerase inhibitor 7‐ethyl‐10‐hydroxyl camptothecin (SN38) to treat GBM. Given a higher surface‐to‐volume ratio, uIONP shows one‐ or three‐folds higher SN38 loading efficiency (48.3 ± 6.1%, mg/mg Fe) than those with core sizes of 10 or 20 nm. SN38 encapsulated in the coating polymer exhibits pH sensitive release with |
| doi_str_mv | 10.1002/adhm.202102816 |
| format | Article |
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Using ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier to deliver insoluble chemotherapy agent, 7‐ethyl‐10‐hydroxyl camptothecin (SN38), to intracranial tumors is reported. With cyclic peptide Arg‐Gly‐Asp‐D‐Phe‐Cys (RGD) as the ligand targeting the tumor integrin, RGD‐uIONP/SN38 exerts tumor specific cytotoxicity to U87MG glioblastoma cells, prolonging survival of mice with glioblastoma.</description><identifier>ISSN: 2192-2640</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.202102816</identifier><identifier>PMID: 35481625</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Angiogenesis ; Animals ; Blood-brain barrier ; Brain cancer ; Brain Neoplasms - drug therapy ; Brain tumors ; Camptothecin ; Cell Line, Tumor ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; DNA topoisomerase ; DNA topoisomerase inhibitors ; drug delivery ; Glioblastoma ; Glioblastoma - drug therapy ; Glucuronosyltransferase ; Inhibitors ; Integrins ; iron oxide nanoparticles ; Iron oxides ; Magnetic Iron Oxide Nanoparticles ; Mice ; Nanomaterials ; Nanoparticles ; Oligopeptides ; pH effects ; SN38 ; theranostics ; Topoisomerase Inhibitors ; Toxicity ; tumor integrin ; Tumors ; Ultrafines</subject><ispartof>Advanced healthcare materials, 2022-07, Vol.11 (14), p.e2102816-n/a</ispartof><rights>2022 Wiley‐VCH GmbH</rights><rights>2022 Wiley-VCH GmbH.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4686-c2280d941cbe4989bc9ac5dd185c716b7938d391dedb087b4c51157cfb5a9f453</citedby><cites>FETCH-LOGICAL-c4686-c2280d941cbe4989bc9ac5dd185c716b7938d391dedb087b4c51157cfb5a9f453</cites><orcidid>0000-0002-0147-6022</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadhm.202102816$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.202102816$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35481625$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Yuancheng</creatorcontrib><creatorcontrib>Xie, Manman</creatorcontrib><creatorcontrib>Jones, Joshua B.</creatorcontrib><creatorcontrib>Zhang, Zhaobin</creatorcontrib><creatorcontrib>Wang, Zi</creatorcontrib><creatorcontrib>Dang, Tu</creatorcontrib><creatorcontrib>Wang, Xinyu</creatorcontrib><creatorcontrib>Lipowska, Malgorzata</creatorcontrib><creatorcontrib>Mao, Hui</creatorcontrib><title>Targeted Delivery of DNA Topoisomerase Inhibitor SN38 to Intracranial Tumors of Glioblastoma Using Sub‐5 Ultrafine Iron Oxide Nanoparticles</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>Effectively delivering therapeutics for treating brain tumors is hindered by the physical and biological barriers in the brain. Even with the compromised blood–brain barrier and highly angiogenic blood–tumor barrier seen in glioblastoma (GBM), most drugs, including nanomaterial‐based formulations, hardly reach intracranial tumors. This work investigates sub‐5 nm ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier for delivering DNA topoisomerase inhibitor 7‐ethyl‐10‐hydroxyl camptothecin (SN38) to treat GBM. Given a higher surface‐to‐volume ratio, uIONP shows one‐ or three‐folds higher SN38 loading efficiency (48.3 ± 6.1%, mg/mg Fe) than those with core sizes of 10 or 20 nm. SN38 encapsulated in the coating polymer exhibits pH sensitive release with <10% over 48 h at pH 7.4, but 86% at pH 5, thus being protected from converting to inactive glucuronide by UDP‐glucuronosyltransferase 1A1. Conjugating αvβ3‐integrin‐targeted cyclo(Arg‐Gly‐Asp‐D‐Phe‐Cys) (RGD) as ligands, RGD‐uIONP/SN38 demonstrates targeted cytotoxicity to αvβ3‐integrin‐overexpressed U87MG GBM cells with a half‐maximal inhibitory concentration (IC50) of 30.9 ± 2.2 nm. The efficacy study using an orthotopic mouse model of GBM reveals tumor‐specific delivery of 11.5% injected RGD‐uIONP/SN38 (10 mg Fe kg−1), significantly prolonging the survival in mice by 41%, comparing to those treated with SN38 alone (p < 0.001).
Using ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier to deliver insoluble chemotherapy agent, 7‐ethyl‐10‐hydroxyl camptothecin (SN38), to intracranial tumors is reported. With cyclic peptide Arg‐Gly‐Asp‐D‐Phe‐Cys (RGD) as the ligand targeting the tumor integrin, RGD‐uIONP/SN38 exerts tumor specific cytotoxicity to U87MG glioblastoma cells, prolonging survival of mice with glioblastoma.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Blood-brain barrier</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain tumors</subject><subject>Camptothecin</subject><subject>Cell Line, Tumor</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA topoisomerase</subject><subject>DNA topoisomerase inhibitors</subject><subject>drug delivery</subject><subject>Glioblastoma</subject><subject>Glioblastoma - drug therapy</subject><subject>Glucuronosyltransferase</subject><subject>Inhibitors</subject><subject>Integrins</subject><subject>iron oxide nanoparticles</subject><subject>Iron oxides</subject><subject>Magnetic Iron Oxide Nanoparticles</subject><subject>Mice</subject><subject>Nanomaterials</subject><subject>Nanoparticles</subject><subject>Oligopeptides</subject><subject>pH effects</subject><subject>SN38</subject><subject>theranostics</subject><subject>Topoisomerase Inhibitors</subject><subject>Toxicity</subject><subject>tumor integrin</subject><subject>Tumors</subject><subject>Ultrafines</subject><issn>2192-2640</issn><issn>2192-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1uEzEUhS0EolXpliWyxDrB9ow99gYpaqCtVNJFk7Xlv0lcecbBnilk1xeoxDPyJDhKCbDibnxln_Pdax0A3mI0xQiRD8puuilBBCPCMXsBTgkWZEIYFS-PfY1OwHnO96gUo5hx_BqcVLQuBkJPwdNSpbUbnIVzF_yDSzsYWzhfzOAybqPPsXNJZQev-43XfogJ3i0qDodYboakTFK9VwEuxy6mvLdeBh91UHmInYKr7Ps1vBv1z8cfFK5CcbS-L7QUe3j73VsHF6qPW5UGb4LLb8CrVoXszp_PM7D6_Gl5cTW5ub28vpjdTEzNOJsYQjiyosZGu1pwoY1QhlqLOTUNZroRFbeVwNZZjXija0Mxpo1pNVWirWl1Bj4euNtRd84at_9LkNvkO5V2Miov_33p_Uau44MUFeJMNAXw_hmQ4tfR5UHexzH1ZWdJmMANE0LwopoeVCbFnJNrjxMwkvsE5T5BeUywGN79vddR_juvIhAHwTcf3O4_ODmbX335A_8FXo6rDg</recordid><startdate>202207</startdate><enddate>202207</enddate><creator>Li, Yuancheng</creator><creator>Xie, Manman</creator><creator>Jones, Joshua B.</creator><creator>Zhang, Zhaobin</creator><creator>Wang, Zi</creator><creator>Dang, Tu</creator><creator>Wang, Xinyu</creator><creator>Lipowska, Malgorzata</creator><creator>Mao, Hui</creator><general>Wiley Subscription Services, Inc</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>7QF</scope><scope>7QP</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T5</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7TO</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0147-6022</orcidid></search><sort><creationdate>202207</creationdate><title>Targeted Delivery of DNA Topoisomerase Inhibitor SN38 to Intracranial Tumors of Glioblastoma Using Sub‐5 Ultrafine Iron Oxide Nanoparticles</title><author>Li, Yuancheng ; 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Even with the compromised blood–brain barrier and highly angiogenic blood–tumor barrier seen in glioblastoma (GBM), most drugs, including nanomaterial‐based formulations, hardly reach intracranial tumors. This work investigates sub‐5 nm ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier for delivering DNA topoisomerase inhibitor 7‐ethyl‐10‐hydroxyl camptothecin (SN38) to treat GBM. Given a higher surface‐to‐volume ratio, uIONP shows one‐ or three‐folds higher SN38 loading efficiency (48.3 ± 6.1%, mg/mg Fe) than those with core sizes of 10 or 20 nm. SN38 encapsulated in the coating polymer exhibits pH sensitive release with <10% over 48 h at pH 7.4, but 86% at pH 5, thus being protected from converting to inactive glucuronide by UDP‐glucuronosyltransferase 1A1. Conjugating αvβ3‐integrin‐targeted cyclo(Arg‐Gly‐Asp‐D‐Phe‐Cys) (RGD) as ligands, RGD‐uIONP/SN38 demonstrates targeted cytotoxicity to αvβ3‐integrin‐overexpressed U87MG GBM cells with a half‐maximal inhibitory concentration (IC50) of 30.9 ± 2.2 nm. The efficacy study using an orthotopic mouse model of GBM reveals tumor‐specific delivery of 11.5% injected RGD‐uIONP/SN38 (10 mg Fe kg−1), significantly prolonging the survival in mice by 41%, comparing to those treated with SN38 alone (p < 0.001).
Using ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier to deliver insoluble chemotherapy agent, 7‐ethyl‐10‐hydroxyl camptothecin (SN38), to intracranial tumors is reported. With cyclic peptide Arg‐Gly‐Asp‐D‐Phe‐Cys (RGD) as the ligand targeting the tumor integrin, RGD‐uIONP/SN38 exerts tumor specific cytotoxicity to U87MG glioblastoma cells, prolonging survival of mice with glioblastoma.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>35481625</pmid><doi>10.1002/adhm.202102816</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-0147-6022</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Animals Blood-brain barrier Brain cancer Brain Neoplasms - drug therapy Brain tumors Camptothecin Cell Line, Tumor Cytotoxicity Deoxyribonucleic acid DNA DNA topoisomerase DNA topoisomerase inhibitors drug delivery Glioblastoma Glioblastoma - drug therapy Glucuronosyltransferase Inhibitors Integrins iron oxide nanoparticles Iron oxides Magnetic Iron Oxide Nanoparticles Mice Nanomaterials Nanoparticles Oligopeptides pH effects SN38 theranostics Topoisomerase Inhibitors Toxicity tumor integrin Tumors Ultrafines |
| title | Targeted Delivery of DNA Topoisomerase Inhibitor SN38 to Intracranial Tumors of Glioblastoma Using Sub‐5 Ultrafine Iron Oxide Nanoparticles |
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