In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons

Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to...
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Autor*in:	Honoka Obata [verfasserIn] Atsushi B. Tsuji [verfasserIn] Hitomi Sudo [verfasserIn] Aya Sugyo [verfasserIn] Katsuyuki Minegishi [verfasserIn] Kotaro Nagatsu [verfasserIn] Mikako Ogawa [verfasserIn] Ming-Rong Zhang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	Auger electron cisplatin radio-drug DNA double-strand break

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 22(2021), 9, p 4622
Übergeordnetes Werk:	volume:22 ; year:2021 ; number:9, p 4622

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms22094622

Katalog-ID:	DOAJ072613009

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allfields	10.3390/ijms22094622 doi (DE-627)DOAJ072613009 (DE-599)DOAJ8c82097bb9d84cd28fe97df478ad0168 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Honoka Obata verfasserin aut In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. Auger electron cisplatin <sup<191</sup<Pt <sup<189</sup<Pt radio-drug DNA double-strand break Biology (General) Chemistry Atsushi B. Tsuji verfasserin aut Hitomi Sudo verfasserin aut Aya Sugyo verfasserin aut Katsuyuki Minegishi verfasserin aut Kotaro Nagatsu verfasserin aut Mikako Ogawa verfasserin aut Ming-Rong Zhang verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 9, p 4622 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:9, p 4622 https://doi.org/10.3390/ijms22094622 kostenfrei https://doaj.org/article/8c82097bb9d84cd28fe97df478ad0168 kostenfrei https://www.mdpi.com/1422-0067/22/9/4622 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 9, p 4622
spelling	10.3390/ijms22094622 doi (DE-627)DOAJ072613009 (DE-599)DOAJ8c82097bb9d84cd28fe97df478ad0168 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Honoka Obata verfasserin aut In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. Auger electron cisplatin <sup<191</sup<Pt <sup<189</sup<Pt radio-drug DNA double-strand break Biology (General) Chemistry Atsushi B. Tsuji verfasserin aut Hitomi Sudo verfasserin aut Aya Sugyo verfasserin aut Katsuyuki Minegishi verfasserin aut Kotaro Nagatsu verfasserin aut Mikako Ogawa verfasserin aut Ming-Rong Zhang verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 9, p 4622 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:9, p 4622 https://doi.org/10.3390/ijms22094622 kostenfrei https://doaj.org/article/8c82097bb9d84cd28fe97df478ad0168 kostenfrei https://www.mdpi.com/1422-0067/22/9/4622 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 9, p 4622
allfields_unstemmed	10.3390/ijms22094622 doi (DE-627)DOAJ072613009 (DE-599)DOAJ8c82097bb9d84cd28fe97df478ad0168 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Honoka Obata verfasserin aut In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. Auger electron cisplatin <sup<191</sup<Pt <sup<189</sup<Pt radio-drug DNA double-strand break Biology (General) Chemistry Atsushi B. Tsuji verfasserin aut Hitomi Sudo verfasserin aut Aya Sugyo verfasserin aut Katsuyuki Minegishi verfasserin aut Kotaro Nagatsu verfasserin aut Mikako Ogawa verfasserin aut Ming-Rong Zhang verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 9, p 4622 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:9, p 4622 https://doi.org/10.3390/ijms22094622 kostenfrei https://doaj.org/article/8c82097bb9d84cd28fe97df478ad0168 kostenfrei https://www.mdpi.com/1422-0067/22/9/4622 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 9, p 4622
allfieldsGer	10.3390/ijms22094622 doi (DE-627)DOAJ072613009 (DE-599)DOAJ8c82097bb9d84cd28fe97df478ad0168 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Honoka Obata verfasserin aut In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. Auger electron cisplatin <sup<191</sup<Pt <sup<189</sup<Pt radio-drug DNA double-strand break Biology (General) Chemistry Atsushi B. Tsuji verfasserin aut Hitomi Sudo verfasserin aut Aya Sugyo verfasserin aut Katsuyuki Minegishi verfasserin aut Kotaro Nagatsu verfasserin aut Mikako Ogawa verfasserin aut Ming-Rong Zhang verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 9, p 4622 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:9, p 4622 https://doi.org/10.3390/ijms22094622 kostenfrei https://doaj.org/article/8c82097bb9d84cd28fe97df478ad0168 kostenfrei https://www.mdpi.com/1422-0067/22/9/4622 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 9, p 4622
allfieldsSound	10.3390/ijms22094622 doi (DE-627)DOAJ072613009 (DE-599)DOAJ8c82097bb9d84cd28fe97df478ad0168 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Honoka Obata verfasserin aut In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<. Auger electron cisplatin <sup<191</sup<Pt <sup<189</sup<Pt radio-drug DNA double-strand break Biology (General) Chemistry Atsushi B. Tsuji verfasserin aut Hitomi Sudo verfasserin aut Aya Sugyo verfasserin aut Katsuyuki Minegishi verfasserin aut Kotaro Nagatsu verfasserin aut Mikako Ogawa verfasserin aut Ming-Rong Zhang verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 9, p 4622 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:9, p 4622 https://doi.org/10.3390/ijms22094622 kostenfrei https://doaj.org/article/8c82097bb9d84cd28fe97df478ad0168 kostenfrei https://www.mdpi.com/1422-0067/22/9/4622 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 9, p 4622
language	English
source	In International Journal of Molecular Sciences 22(2021), 9, p 4622 volume:22 year:2021 number:9, p 4622
sourceStr	In International Journal of Molecular Sciences 22(2021), 9, p 4622 volume:22 year:2021 number:9, p 4622
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Auger electron cisplatin <sup<191</sup<Pt <sup<189</sup<Pt radio-drug DNA double-strand break Biology (General) Chemistry
isfreeaccess_bool	true
container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Honoka Obata @@aut@@ Atsushi B. Tsuji @@aut@@ Hitomi Sudo @@aut@@ Aya Sugyo @@aut@@ Katsuyuki Minegishi @@aut@@ Kotaro Nagatsu @@aut@@ Mikako Ogawa @@aut@@ Ming-Rong Zhang @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	316340715
id	DOAJ072613009
language_de	englisch
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callnumber-first	Q - Science
author	Honoka Obata
spellingShingle	Honoka Obata misc QH301-705.5 misc QD1-999 misc Auger electron misc cisplatin misc <sup<191</sup<Pt misc <sup<189</sup<Pt misc radio-drug misc DNA double-strand break misc Biology (General) misc Chemistry In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons
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topic_title	QH301-705.5 QD1-999 In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons Auger electron cisplatin <sup<191</sup<Pt <sup<189</sup<Pt radio-drug DNA double-strand break
topic	misc QH301-705.5 misc QD1-999 misc Auger electron misc cisplatin misc <sup<191</sup<Pt misc <sup<189</sup<Pt misc radio-drug misc DNA double-strand break misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc Auger electron misc cisplatin misc <sup<191</sup<Pt misc <sup<189</sup<Pt misc radio-drug misc DNA double-strand break misc Biology (General) misc Chemistry
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title	In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons
ctrlnum	(DE-627)DOAJ072613009 (DE-599)DOAJ8c82097bb9d84cd28fe97df478ad0168
title_full	In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons
author_sort	Honoka Obata
journal	International Journal of Molecular Sciences
journalStr	International Journal of Molecular Sciences
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author_browse	Honoka Obata Atsushi B. Tsuji Hitomi Sudo Aya Sugyo Katsuyuki Minegishi Kotaro Nagatsu Mikako Ogawa Ming-Rong Zhang
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author-letter	Honoka Obata
doi_str_mv	10.3390/ijms22094622
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title_sort	in vitro evaluation of no-carrier-added radiolabeled cisplatin ([<sup<189, 191</sup<pt]cisplatin) emitting auger electrons
callnumber	QH301-705.5
title_auth	In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons
abstract	Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<.
abstractGer	Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<.
abstract_unstemmed	Due to their short-range (2–500 nm), Auger electrons (Auger <i<e<sup<−</sup<</i<) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger <i<e</i<<sup<−</sup<, it remains challenging to maximize the interaction between Auger <i<e</i<<sup<−</sup< and DNA. To assess the DNA-damaging effect of Auger <i<e</i<<sup<−</sup< released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [<sup<189, 191</sup<Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger <i<e</i<<sup<−</sup< very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger <i<e</i<<sup<−</sup<.
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title_short	In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons
url	https://doi.org/10.3390/ijms22094622 https://doaj.org/article/8c82097bb9d84cd28fe97df478ad0168 https://www.mdpi.com/1422-0067/22/9/4622 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067
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In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([<sup<189, 191</sup<Pt]cisplatin) Emitting Auger Electrons

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