Cubosome nanoparticles for enhanced delivery of mitochondria anticancer drug elesclomol and therapeutic monitoring via sub-cellular NAD(P)H multi-photon fluorescence lifetime imaging
Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen species. Here, for the first time, we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized with Pluronic F127. Cellular uptake and nanocarrier accumulation close to the mitoc...
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| Veröffentlicht in: | Nano research 2019-05, Vol.12 (5), p.991-998 |
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| creator | Faria, Ana R. Silvestre, Oscar F. Maibohm, Christian Adão, Ricardo M. R. Silva, Bruno F. B. Nieder, Jana B. |
| description | Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen species. Here, for the first time, we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized with Pluronic F127. Cellular uptake and nanocarrier accumulation close to the mitochondria with sub-micrometer distance is identified via three-dimensional (3D) confocal microscopy and edge-to-edge compartment analysis. To monitor the therapeutic effect of the ELC nanocarrier, we apply for the first time, label-free time-lapse multi-photon fluorescence lifetime imaging microscopy (MP-FLIM) to track NAD(P)H cofactors with sub-cellular resolution on live cells exposed to an anticancer nanocarrier. Improved
in vitro
cytotoxicity is verified when loading the pre-complexed ELC with copper (ELC-Cu). Importantly, for equivalent copper concentration, cubosomes loaded with ELC-Cu show higher cytotoxicity compared to the free drug. The novel nanocarrier shows promising features for systemic ELC-Cu administration, and furthermore we establish the MP-FLIM technique for the assessment of anticancer drug delivery systems. |
| doi_str_mv | 10.1007/s12274-018-2231-5 |
| format | Article |
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in vitro
cytotoxicity is verified when loading the pre-complexed ELC with copper (ELC-Cu). Importantly, for equivalent copper concentration, cubosomes loaded with ELC-Cu show higher cytotoxicity compared to the free drug. The novel nanocarrier shows promising features for systemic ELC-Cu administration, and furthermore we establish the MP-FLIM technique for the assessment of anticancer drug delivery systems.</description><identifier>ISSN: 1998-0124</identifier><identifier>EISSN: 1998-0000</identifier><identifier>DOI: 10.1007/s12274-018-2231-5</identifier><language>eng</language><publisher>Beijing: Tsinghua University Press</publisher><subject>Atomic/Molecular Structure and Spectra ; Biomedicine ; Biotechnology ; Cancer ; Chemistry and Materials Science ; Chemotherapy ; Cofactors ; Condensed Matter Physics ; Confocal microscopy ; Copper ; Cytotoxicity ; Drug delivery ; Drug delivery systems ; Fluorescence ; Materials Science ; Microscopy ; Mitochondria ; NAD ; Nanoparticles ; Nanotechnology ; Photons ; Poloxamers ; Reactive oxygen species ; Research Article ; Toxicity</subject><ispartof>Nano research, 2019-05, Vol.12 (5), p.991-998</ispartof><rights>Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018</rights><rights>Nano Research is a copyright of Springer, (2018). All Rights Reserved.</rights><rights>Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c344t-f1165b0c68cbdcb0fdb59ad8a50191b20987cf9ebbcafb43e6662721df6ec71c3</citedby><cites>FETCH-LOGICAL-c344t-f1165b0c68cbdcb0fdb59ad8a50191b20987cf9ebbcafb43e6662721df6ec71c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12274-018-2231-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12274-018-2231-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids></links><search><creatorcontrib>Faria, Ana R.</creatorcontrib><creatorcontrib>Silvestre, Oscar F.</creatorcontrib><creatorcontrib>Maibohm, Christian</creatorcontrib><creatorcontrib>Adão, Ricardo M. R.</creatorcontrib><creatorcontrib>Silva, Bruno F. B.</creatorcontrib><creatorcontrib>Nieder, Jana B.</creatorcontrib><title>Cubosome nanoparticles for enhanced delivery of mitochondria anticancer drug elesclomol and therapeutic monitoring via sub-cellular NAD(P)H multi-photon fluorescence lifetime imaging</title><title>Nano research</title><addtitle>Nano Res</addtitle><description>Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen species. Here, for the first time, we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized with Pluronic F127. Cellular uptake and nanocarrier accumulation close to the mitochondria with sub-micrometer distance is identified via three-dimensional (3D) confocal microscopy and edge-to-edge compartment analysis. To monitor the therapeutic effect of the ELC nanocarrier, we apply for the first time, label-free time-lapse multi-photon fluorescence lifetime imaging microscopy (MP-FLIM) to track NAD(P)H cofactors with sub-cellular resolution on live cells exposed to an anticancer nanocarrier. Improved
in vitro
cytotoxicity is verified when loading the pre-complexed ELC with copper (ELC-Cu). Importantly, for equivalent copper concentration, cubosomes loaded with ELC-Cu show higher cytotoxicity compared to the free drug. The novel nanocarrier shows promising features for systemic ELC-Cu administration, and furthermore we establish the MP-FLIM technique for the assessment of anticancer drug delivery systems.</description><subject>Atomic/Molecular Structure and Spectra</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Chemistry and Materials Science</subject><subject>Chemotherapy</subject><subject>Cofactors</subject><subject>Condensed Matter Physics</subject><subject>Confocal microscopy</subject><subject>Copper</subject><subject>Cytotoxicity</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Fluorescence</subject><subject>Materials Science</subject><subject>Microscopy</subject><subject>Mitochondria</subject><subject>NAD</subject><subject>Nanoparticles</subject><subject>Nanotechnology</subject><subject>Photons</subject><subject>Poloxamers</subject><subject>Reactive oxygen species</subject><subject>Research Article</subject><subject>Toxicity</subject><issn>1998-0124</issn><issn>1998-0000</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc1uFSEYhifGJtbWC3BH4kYXKDDDzLBsjtWaNNqFrgk_H-fQMDDC0KQ31uuTk6NxpWwg4Xleft6ue03Je0rI9KFQxqYBEzpjxnqK-bPunAoxY9LG8z9ryoYX3ctS7gkZGR3m8-5pV3UqaQEUVUyryps3AQpyKSOIBxUNWGQh-AfIjyg5tPgtmUOKNnuFVGz4kcnI5rpH0FQT0pJC27JoO0BWK9QGoSXFZmYf9-ihmaVqbCCEGlRGX68-vr17d4OWGjaP10PaUkQu1JRbHLR4FLyDzbdb-kXtW8Zld-ZUKPDq93zR_fh0_X13g2-_ff6yu7rFph-GDTtKR66JGWejrdHEWc2FsrPihAqqGRHzZJwArY1yeuhhHEc2MWrdCGaipr_o3pxy15x-ViibvE81x3akZJz0vOezEP-laE95LwQhjaInyuRUSgYn19yekx8lJfJYojyVKFuJ8lii5M1hJ6esx6-D_Df539IvLKekKA</recordid><startdate>20190501</startdate><enddate>20190501</enddate><creator>Faria, Ana R.</creator><creator>Silvestre, Oscar F.</creator><creator>Maibohm, Christian</creator><creator>Adão, Ricardo M. 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B. ; Nieder, Jana B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-f1165b0c68cbdcb0fdb59ad8a50191b20987cf9ebbcafb43e6662721df6ec71c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Atomic/Molecular Structure and Spectra</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Chemistry and Materials Science</topic><topic>Chemotherapy</topic><topic>Cofactors</topic><topic>Condensed Matter Physics</topic><topic>Confocal microscopy</topic><topic>Copper</topic><topic>Cytotoxicity</topic><topic>Drug delivery</topic><topic>Drug delivery systems</topic><topic>Fluorescence</topic><topic>Materials Science</topic><topic>Microscopy</topic><topic>Mitochondria</topic><topic>NAD</topic><topic>Nanoparticles</topic><topic>Nanotechnology</topic><topic>Photons</topic><topic>Poloxamers</topic><topic>Reactive oxygen species</topic><topic>Research Article</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Faria, Ana R.</creatorcontrib><creatorcontrib>Silvestre, Oscar F.</creatorcontrib><creatorcontrib>Maibohm, Christian</creatorcontrib><creatorcontrib>Adão, Ricardo M. 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R.</au><au>Silva, Bruno F. B.</au><au>Nieder, Jana B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cubosome nanoparticles for enhanced delivery of mitochondria anticancer drug elesclomol and therapeutic monitoring via sub-cellular NAD(P)H multi-photon fluorescence lifetime imaging</atitle><jtitle>Nano research</jtitle><stitle>Nano Res</stitle><date>2019-05-01</date><risdate>2019</risdate><volume>12</volume><issue>5</issue><spage>991</spage><epage>998</epage><pages>991-998</pages><issn>1998-0124</issn><eissn>1998-0000</eissn><abstract>Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen species. Here, for the first time, we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized with Pluronic F127. Cellular uptake and nanocarrier accumulation close to the mitochondria with sub-micrometer distance is identified via three-dimensional (3D) confocal microscopy and edge-to-edge compartment analysis. To monitor the therapeutic effect of the ELC nanocarrier, we apply for the first time, label-free time-lapse multi-photon fluorescence lifetime imaging microscopy (MP-FLIM) to track NAD(P)H cofactors with sub-cellular resolution on live cells exposed to an anticancer nanocarrier. Improved
in vitro
cytotoxicity is verified when loading the pre-complexed ELC with copper (ELC-Cu). Importantly, for equivalent copper concentration, cubosomes loaded with ELC-Cu show higher cytotoxicity compared to the free drug. The novel nanocarrier shows promising features for systemic ELC-Cu administration, and furthermore we establish the MP-FLIM technique for the assessment of anticancer drug delivery systems.</abstract><cop>Beijing</cop><pub>Tsinghua University Press</pub><doi>10.1007/s12274-018-2231-5</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1998-0124 |
| ispartof | Nano research, 2019-05, Vol.12 (5), p.991-998 |
| issn | 1998-0124 1998-0000 |
| language | eng |
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| subjects | Atomic/Molecular Structure and Spectra Biomedicine Biotechnology Cancer Chemistry and Materials Science Chemotherapy Cofactors Condensed Matter Physics Confocal microscopy Copper Cytotoxicity Drug delivery Drug delivery systems Fluorescence Materials Science Microscopy Mitochondria NAD Nanoparticles Nanotechnology Photons Poloxamers Reactive oxygen species Research Article Toxicity |
| title | Cubosome nanoparticles for enhanced delivery of mitochondria anticancer drug elesclomol and therapeutic monitoring via sub-cellular NAD(P)H multi-photon fluorescence lifetime imaging |
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