Ultrasmall Nanoparticle Delivery of Doxorubicin Improves Therapeutic Index for High-Grade Glioma
Despite dramatic growth in the number of small-molecule drugs developed to treat solid tumors, durable therapeutic options to control primary central nervous system malignancies are relatively scarce. Chemotherapeutic agents that appear biologically potent in model systems have often been found to b...
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| Veröffentlicht in: | Clinical cancer research 2022-07, Vol.28 (13), p.2938-2952 |
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| creator | Aragon-Sanabria, Virginia Aditya, Anusha Zhang, Li Chen, Feng Yoo, Barney Cao, Tianye Madajewski, Brian Lee, Rachel Turker, Melik Z Ma, Kai Monette, Sebastien Chen, Peiming Wu, Jing Ruan, Shutian Overholtzer, Michael Zanzonico, Pat Rudin, Charles M Brennan, Cameron Wiesner, Ulrich Bradbury, Michelle S |
| description | Despite dramatic growth in the number of small-molecule drugs developed to treat solid tumors, durable therapeutic options to control primary central nervous system malignancies are relatively scarce. Chemotherapeutic agents that appear biologically potent in model systems have often been found to be marginally effective at best when given systemically in clinical trials. This work presents for the first time an ultrasmall ( |
| doi_str_mv | 10.1158/1078-0432.CCR-21-4053 |
| format | Article |
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This work presents first-in-kind renally clearable ultrasmall (<8 nm) multimodal C' dots with surface-conjugated doxorubicin (DOX) via pH-sensitive linkers for the efficacious treatment in two different clinically relevant high-grade glioma models.
Optimal drug-per-particle ratios of as-developed nanoparticle-drug conjugates were established and used to obtain favorable pharmacokinetic profiles. The in vivo efficacy results showed significantly improved biological, therapeutic, and toxicological properties over the native drug after intravenous administration in platelet-derived growth factor-driven genetically engineered mouse model, and an EGF-expressing patient-derived xenograft (EGFR PDX) model.
Ultrasmall C' dot-drug conjugates showed great translational potential over DOX for improving the therapeutic outcome of patients with high-grade gliomas, even without a cancer-targeting moiety.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-21-4053</identifier><identifier>PMID: 35499557</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Cell Line, Tumor ; Doxorubicin ; Drug Delivery Systems - methods ; Glioma - drug therapy ; Humans ; Mice ; Nanoparticles ; Silicon Dioxide ; Therapeutic Index</subject><ispartof>Clinical cancer research, 2022-07, Vol.28 (13), p.2938-2952</ispartof><rights>2022 The Authors; Published by the American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-88ba1502b48a6c421b05a7a5a5d092e400eb4428ec082722ab3d01f3839888ea3</citedby><cites>FETCH-LOGICAL-c411t-88ba1502b48a6c421b05a7a5a5d092e400eb4428ec082722ab3d01f3839888ea3</cites><orcidid>0000-0001-7801-4275 ; 0000-0001-5204-3465 ; 0000-0003-4864-4334 ; 0000-0003-4064-8891 ; 0000-0002-2556-1619 ; 0000-0003-2841-6887 ; 0000-0003-1743-3980</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35499557$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aragon-Sanabria, Virginia</creatorcontrib><creatorcontrib>Aditya, Anusha</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Chen, Feng</creatorcontrib><creatorcontrib>Yoo, Barney</creatorcontrib><creatorcontrib>Cao, Tianye</creatorcontrib><creatorcontrib>Madajewski, Brian</creatorcontrib><creatorcontrib>Lee, Rachel</creatorcontrib><creatorcontrib>Turker, Melik Z</creatorcontrib><creatorcontrib>Ma, Kai</creatorcontrib><creatorcontrib>Monette, Sebastien</creatorcontrib><creatorcontrib>Chen, Peiming</creatorcontrib><creatorcontrib>Wu, Jing</creatorcontrib><creatorcontrib>Ruan, Shutian</creatorcontrib><creatorcontrib>Overholtzer, Michael</creatorcontrib><creatorcontrib>Zanzonico, Pat</creatorcontrib><creatorcontrib>Rudin, Charles M</creatorcontrib><creatorcontrib>Brennan, Cameron</creatorcontrib><creatorcontrib>Wiesner, Ulrich</creatorcontrib><creatorcontrib>Bradbury, Michelle S</creatorcontrib><title>Ultrasmall Nanoparticle Delivery of Doxorubicin Improves Therapeutic Index for High-Grade Glioma</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Despite dramatic growth in the number of small-molecule drugs developed to treat solid tumors, durable therapeutic options to control primary central nervous system malignancies are relatively scarce. Chemotherapeutic agents that appear biologically potent in model systems have often been found to be marginally effective at best when given systemically in clinical trials. This work presents for the first time an ultrasmall (<8 nm) multimodal core-shell silica nanoparticle, Cornell prime dots (or C' dots), for the efficacious treatment of high-grade gliomas.
This work presents first-in-kind renally clearable ultrasmall (<8 nm) multimodal C' dots with surface-conjugated doxorubicin (DOX) via pH-sensitive linkers for the efficacious treatment in two different clinically relevant high-grade glioma models.
Optimal drug-per-particle ratios of as-developed nanoparticle-drug conjugates were established and used to obtain favorable pharmacokinetic profiles. The in vivo efficacy results showed significantly improved biological, therapeutic, and toxicological properties over the native drug after intravenous administration in platelet-derived growth factor-driven genetically engineered mouse model, and an EGF-expressing patient-derived xenograft (EGFR PDX) model.
Ultrasmall C' dot-drug conjugates showed great translational potential over DOX for improving the therapeutic outcome of patients with high-grade gliomas, even without a cancer-targeting moiety.</description><subject>Animals</subject><subject>Cell Line, Tumor</subject><subject>Doxorubicin</subject><subject>Drug Delivery Systems - methods</subject><subject>Glioma - drug therapy</subject><subject>Humans</subject><subject>Mice</subject><subject>Nanoparticles</subject><subject>Silicon Dioxide</subject><subject>Therapeutic Index</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkN1OwkAQhTdGI4g-gmZfoLi_dHtjYkCBxGhi4HqdtltYs-02WyDw9rZBiF7NJHPOmZwPoXtKhpRK9UhJrCIiOBuOx58Ro5Egkl-gPpUyjjgbyct2P2l66KZpvgmhghJxjXpciiRphX30tXSbAE0JzuF3qHwNYWMzZ_DEOLsz4YB9gSd-78M2tZmt8Lysg9-ZBi_WJkBttq0cz6vc7HHhA57Z1TqaBsgNnjrrS7hFVwW4xtz9zgFavr4sxrPo7WM6Hz-_RZmgdBMplQKVhKVCwSgTjKZEQgwSZE4SZgQhJhWCKZMRxWLGIOU5oQVXPFFKGeAD9HTMrbdpafLMVG0vp-tgSwgH7cHq_5fKrvXK73TCJBkJ1gbIY0AWfNMEU5y9lOgOue5w6g6nbpFrRnWHvPU9_H18dp0Y8x8Fu37U</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Aragon-Sanabria, Virginia</creator><creator>Aditya, Anusha</creator><creator>Zhang, Li</creator><creator>Chen, Feng</creator><creator>Yoo, Barney</creator><creator>Cao, Tianye</creator><creator>Madajewski, Brian</creator><creator>Lee, Rachel</creator><creator>Turker, Melik Z</creator><creator>Ma, Kai</creator><creator>Monette, Sebastien</creator><creator>Chen, Peiming</creator><creator>Wu, Jing</creator><creator>Ruan, Shutian</creator><creator>Overholtzer, Michael</creator><creator>Zanzonico, Pat</creator><creator>Rudin, Charles M</creator><creator>Brennan, Cameron</creator><creator>Wiesner, Ulrich</creator><creator>Bradbury, Michelle S</creator><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>5PM</scope><orcidid>https://orcid.org/0000-0001-7801-4275</orcidid><orcidid>https://orcid.org/0000-0001-5204-3465</orcidid><orcidid>https://orcid.org/0000-0003-4864-4334</orcidid><orcidid>https://orcid.org/0000-0003-4064-8891</orcidid><orcidid>https://orcid.org/0000-0002-2556-1619</orcidid><orcidid>https://orcid.org/0000-0003-2841-6887</orcidid><orcidid>https://orcid.org/0000-0003-1743-3980</orcidid></search><sort><creationdate>20220701</creationdate><title>Ultrasmall Nanoparticle Delivery of Doxorubicin Improves Therapeutic Index for High-Grade Glioma</title><author>Aragon-Sanabria, Virginia ; Aditya, Anusha ; Zhang, Li ; Chen, Feng ; Yoo, Barney ; Cao, Tianye ; Madajewski, Brian ; Lee, Rachel ; Turker, Melik Z ; Ma, Kai ; Monette, Sebastien ; Chen, Peiming ; Wu, Jing ; Ruan, Shutian ; Overholtzer, Michael ; Zanzonico, Pat ; Rudin, Charles M ; Brennan, Cameron ; Wiesner, Ulrich ; Bradbury, Michelle S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-88ba1502b48a6c421b05a7a5a5d092e400eb4428ec082722ab3d01f3839888ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Cell Line, Tumor</topic><topic>Doxorubicin</topic><topic>Drug Delivery Systems - methods</topic><topic>Glioma - drug therapy</topic><topic>Humans</topic><topic>Mice</topic><topic>Nanoparticles</topic><topic>Silicon Dioxide</topic><topic>Therapeutic Index</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aragon-Sanabria, Virginia</creatorcontrib><creatorcontrib>Aditya, Anusha</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><creatorcontrib>Chen, Feng</creatorcontrib><creatorcontrib>Yoo, Barney</creatorcontrib><creatorcontrib>Cao, Tianye</creatorcontrib><creatorcontrib>Madajewski, Brian</creatorcontrib><creatorcontrib>Lee, Rachel</creatorcontrib><creatorcontrib>Turker, Melik Z</creatorcontrib><creatorcontrib>Ma, Kai</creatorcontrib><creatorcontrib>Monette, Sebastien</creatorcontrib><creatorcontrib>Chen, Peiming</creatorcontrib><creatorcontrib>Wu, Jing</creatorcontrib><creatorcontrib>Ruan, Shutian</creatorcontrib><creatorcontrib>Overholtzer, Michael</creatorcontrib><creatorcontrib>Zanzonico, Pat</creatorcontrib><creatorcontrib>Rudin, Charles M</creatorcontrib><creatorcontrib>Brennan, Cameron</creatorcontrib><creatorcontrib>Wiesner, Ulrich</creatorcontrib><creatorcontrib>Bradbury, Michelle S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aragon-Sanabria, Virginia</au><au>Aditya, Anusha</au><au>Zhang, Li</au><au>Chen, Feng</au><au>Yoo, Barney</au><au>Cao, Tianye</au><au>Madajewski, Brian</au><au>Lee, Rachel</au><au>Turker, Melik Z</au><au>Ma, Kai</au><au>Monette, Sebastien</au><au>Chen, Peiming</au><au>Wu, Jing</au><au>Ruan, Shutian</au><au>Overholtzer, Michael</au><au>Zanzonico, Pat</au><au>Rudin, Charles M</au><au>Brennan, Cameron</au><au>Wiesner, Ulrich</au><au>Bradbury, Michelle S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ultrasmall Nanoparticle Delivery of Doxorubicin Improves Therapeutic Index for High-Grade Glioma</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2022-07-01</date><risdate>2022</risdate><volume>28</volume><issue>13</issue><spage>2938</spage><epage>2952</epage><pages>2938-2952</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Despite dramatic growth in the number of small-molecule drugs developed to treat solid tumors, durable therapeutic options to control primary central nervous system malignancies are relatively scarce. Chemotherapeutic agents that appear biologically potent in model systems have often been found to be marginally effective at best when given systemically in clinical trials. This work presents for the first time an ultrasmall (<8 nm) multimodal core-shell silica nanoparticle, Cornell prime dots (or C' dots), for the efficacious treatment of high-grade gliomas.
This work presents first-in-kind renally clearable ultrasmall (<8 nm) multimodal C' dots with surface-conjugated doxorubicin (DOX) via pH-sensitive linkers for the efficacious treatment in two different clinically relevant high-grade glioma models.
Optimal drug-per-particle ratios of as-developed nanoparticle-drug conjugates were established and used to obtain favorable pharmacokinetic profiles. The in vivo efficacy results showed significantly improved biological, therapeutic, and toxicological properties over the native drug after intravenous administration in platelet-derived growth factor-driven genetically engineered mouse model, and an EGF-expressing patient-derived xenograft (EGFR PDX) model.
Ultrasmall C' dot-drug conjugates showed great translational potential over DOX for improving the therapeutic outcome of patients with high-grade gliomas, even without a cancer-targeting moiety.</abstract><cop>United States</cop><pmid>35499557</pmid><doi>10.1158/1078-0432.CCR-21-4053</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-7801-4275</orcidid><orcidid>https://orcid.org/0000-0001-5204-3465</orcidid><orcidid>https://orcid.org/0000-0003-4864-4334</orcidid><orcidid>https://orcid.org/0000-0003-4064-8891</orcidid><orcidid>https://orcid.org/0000-0002-2556-1619</orcidid><orcidid>https://orcid.org/0000-0003-2841-6887</orcidid><orcidid>https://orcid.org/0000-0003-1743-3980</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical cancer research, 2022-07, Vol.28 (13), p.2938-2952 |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Cell Line, Tumor Doxorubicin Drug Delivery Systems - methods Glioma - drug therapy Humans Mice Nanoparticles Silicon Dioxide Therapeutic Index |
| title | Ultrasmall Nanoparticle Delivery of Doxorubicin Improves Therapeutic Index for High-Grade Glioma |
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