Au@Pd core–shell nanoparticle conjugated to trastuzumab for the therapy of HER2+ cancers : studies on the applicability of Pd/Ag in vivo generator in combined auger electron therapy

2023
journal article
article
dc.abstract.enBackground. In radionuclide therapy, to enhance therapeutic efficacy, an intriguing alternative is to ensure the simultaneous implementation of low- and high-LET radiation emitted from a one radionuclide. In the present study, we introduce the concept of utilizing $^{109}$Pd (T$_{1/2}$ = 13.7 h) in the form of a $^{109}$Pd/$^{109m}$Ag in vivo generator. In this system, $^{109}$Pd emits beta particles of medium energy, while $^{109m}$Ag releases a cascade of conversion and Auger electrons. $^{109}$Pd was utilized in the form of 15 nm gold nanoparticles, which were coated with a monolayer of $^{109}$Pd. In this system, the $^{109}$Pd atoms are on the surface of the nanoparticle, while the $^{109m}$Ag atoms generated in the decay reaction possess the capability for unhindered emission of Auger electrons. Results. $^{109}$Pd, obtained through neutron irradiation of natural palladium, was deposited onto 15-nm gold nanoparticles, exceeding a efficiency rate of 95%. In contrast to previously published data on in vivo generators based on chelators, where the daughter radionuclide diffuses away from the molecules, daughter radionuclide $^{109m}$Ag remains on the surface of gold nanoparticles after the decay of $^{109}$Pd. To obtain a radiobioconjugate with an affinity for HER2 receptors, polyethylene glycol chains and the monoclonal antibody trastuzumab were attached to the Au@Pd nanoparticles. The synthesized bioconjugate contained an average of 9.5 trastuzumab molecules per one nanoparticle. In vitro cell studies indicated specific binding of the Au@$^{109}$Pd-PEG-trastuzumab radiobioconjugate to the HER2 receptor on SKOV-3 cells, resulting in 90% internalization. Confocal images illustrated the accumulation of Au@$^{109}$Pd-PEG-trastuzumab in the perinuclear area surrounding the cell nucleus. Despite the lack of nuclear localization, which is necessary to achieve an effective cytotoxic effect of Auger electrons, a substantial cytotoxic effect, significantly greater than that of pure β$^{−}$ and pure Auger electron emitters was observed. We hypothesize that in the studied system, the cytotoxic effect of the Auger electrons could have also occurred through the damage to the cell’s nuclear membrane by Auger electrons emitted from nanoparticles accumulated in the perinuclear area. Conclusion. The obtained results show that trastuzumab-functionalized $^{109}$Pd-labeled nanoparticles can be suitable for the application in combined β$^{−}$—Auger electron targeted radionuclide therapy. Due to both components decay (β$^{−}$ and conversion/Auger electrons), the $^{109}$Pd/$^{109m}$Ag in vivo generator presents unique potential in this field. Despite the lack of nuclear localization, which is highly required for efficient Auger electron therapy, an adequate cytotoxic effect was attained.pl
dc.affiliationWydział Fizyki, Astronomii i Informatyki Stosowanej : Instytut Fizyki im. Mariana Smoluchowskiegopl
dc.contributor.authorAbbasi Gharibkandi, Nasrin Abbasi Gharibkandipl
dc.contributor.authorWawrowicz, Kamil - 480195 pl
dc.contributor.authorMajkowska-Pilip, Agnieszkapl
dc.contributor.authorŻelechowska-Matysiak, Kingapl
dc.contributor.authorWierzbicki, Mateuszpl
dc.contributor.authorBilewicz, Aleksanderpl
dc.date.accessioned2024-01-18T12:09:11Z
dc.date.available2024-01-18T12:09:11Z
dc.date.issued2023pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number1pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume8pl
dc.identifier.articleid26pl
dc.identifier.doi10.1186/s41181-023-00212-4pl
dc.identifier.eissn2365-421Xpl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/325769
dc.languageengpl
dc.language.containerengpl
dc.pbn.affiliationDziedzina nauk ścisłych i przyrodniczych : nauki fizycznepl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeotwarte czasopismo
dc.subject.en$^{109}$Pd/$^{109m}$Ag in vivo generatorpl
dc.subject.enradioimmunotherapypl
dc.subject.enauger electron therapypl
dc.subject.ennanotechnologypl
dc.subtypeArticlepl
dc.titleAu@$^{109}$Pd core–shell nanoparticle conjugated to trastuzumab for the therapy of HER2+ cancers : studies on the applicability of $^{109}$Pd/$^{109m}$Ag in vivo generator in combined $\beta^{–}$ auger electron therapypl
dc.title.journalEJNMMI Radiopharmacy and Chemistrypl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
Background. In radionuclide therapy, to enhance therapeutic efficacy, an intriguing alternative is to ensure the simultaneous implementation of low- and high-LET radiation emitted from a one radionuclide. In the present study, we introduce the concept of utilizing $^{109}$Pd (T$_{1/2}$ = 13.7 h) in the form of a $^{109}$Pd/$^{109m}$Ag in vivo generator. In this system, $^{109}$Pd emits beta particles of medium energy, while $^{109m}$Ag releases a cascade of conversion and Auger electrons. $^{109}$Pd was utilized in the form of 15 nm gold nanoparticles, which were coated with a monolayer of $^{109}$Pd. In this system, the $^{109}$Pd atoms are on the surface of the nanoparticle, while the $^{109m}$Ag atoms generated in the decay reaction possess the capability for unhindered emission of Auger electrons. Results. $^{109}$Pd, obtained through neutron irradiation of natural palladium, was deposited onto 15-nm gold nanoparticles, exceeding a efficiency rate of 95%. In contrast to previously published data on in vivo generators based on chelators, where the daughter radionuclide diffuses away from the molecules, daughter radionuclide $^{109m}$Ag remains on the surface of gold nanoparticles after the decay of $^{109}$Pd. To obtain a radiobioconjugate with an affinity for HER2 receptors, polyethylene glycol chains and the monoclonal antibody trastuzumab were attached to the Au@Pd nanoparticles. The synthesized bioconjugate contained an average of 9.5 trastuzumab molecules per one nanoparticle. In vitro cell studies indicated specific binding of the Au@$^{109}$Pd-PEG-trastuzumab radiobioconjugate to the HER2 receptor on SKOV-3 cells, resulting in 90% internalization. Confocal images illustrated the accumulation of Au@$^{109}$Pd-PEG-trastuzumab in the perinuclear area surrounding the cell nucleus. Despite the lack of nuclear localization, which is necessary to achieve an effective cytotoxic effect of Auger electrons, a substantial cytotoxic effect, significantly greater than that of pure β$^{−}$ and pure Auger electron emitters was observed. We hypothesize that in the studied system, the cytotoxic effect of the Auger electrons could have also occurred through the damage to the cell’s nuclear membrane by Auger electrons emitted from nanoparticles accumulated in the perinuclear area. Conclusion. The obtained results show that trastuzumab-functionalized $^{109}$Pd-labeled nanoparticles can be suitable for the application in combined β$^{−}$—Auger electron targeted radionuclide therapy. Due to both components decay (β$^{−}$ and conversion/Auger electrons), the $^{109}$Pd/$^{109m}$Ag in vivo generator presents unique potential in this field. Despite the lack of nuclear localization, which is highly required for efficient Auger electron therapy, an adequate cytotoxic effect was attained.
dc.affiliationpl
Wydział Fizyki, Astronomii i Informatyki Stosowanej : Instytut Fizyki im. Mariana Smoluchowskiego
dc.contributor.authorpl
Abbasi Gharibkandi, Nasrin Abbasi Gharibkandi
dc.contributor.authorpl
Wawrowicz, Kamil - 480195
dc.contributor.authorpl
Majkowska-Pilip, Agnieszka
dc.contributor.authorpl
Żelechowska-Matysiak, Kinga
dc.contributor.authorpl
Wierzbicki, Mateusz
dc.contributor.authorpl
Bilewicz, Aleksander
dc.date.accessioned
2024-01-18T12:09:11Z
dc.date.available
2024-01-18T12:09:11Z
dc.date.issuedpl
2023
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
1
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
8
dc.identifier.articleidpl
26
dc.identifier.doipl
10.1186/s41181-023-00212-4
dc.identifier.eissnpl
2365-421X
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/325769
dc.languagepl
eng
dc.language.containerpl
eng
dc.pbn.affiliationpl
Dziedzina nauk ścisłych i przyrodniczych : nauki fizyczne
dc.rights*
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri*
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
otwarte czasopismo
dc.subject.enpl
$^{109}$Pd/$^{109m}$Ag in vivo generator
dc.subject.enpl
radioimmunotherapy
dc.subject.enpl
auger electron therapy
dc.subject.enpl
nanotechnology
dc.subtypepl
Article
dc.titlepl
Au@$^{109}$Pd core–shell nanoparticle conjugated to trastuzumab for the therapy of HER2+ cancers : studies on the applicability of $^{109}$Pd/$^{109m}$Ag in vivo generator in combined $\beta^{–}$ auger electron therapy
dc.title.journalpl
EJNMMI Radiopharmacy and Chemistry
dc.typepl
JournalArticle
dspace.entity.type
Publication
Affiliations

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