Au@Pt Core-Shell Nanoparticle Bioconjugates for the Therapy of HER2+ Breast Cancer and Hepatocellular Carcinoma. Model Studies on the Applicability of <sup>193m</sup>Pt and <sup>195m</sup>Pt Radionuclides in Auger Electron Therapy
<sup>193m</sup>Pt and <sup>195m</sup>Pt radionuclides are therapeutically attractive Auger electron emitters with notably high Auger electron yield per decay. The present paper summarizes the first step of research on the applications of core-shell (Au@Pt) nanoparticles for e...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-04-01
|
Series: | Molecules |
Subjects: | |
Online Access: | https://www.mdpi.com/1420-3049/26/7/2051 |
_version_ | 1797538895538159616 |
---|---|
author | Kamil Wawrowicz Agnieszka Majkowska-Pilip Damian Gaweł Ewelina Chajduk Tadeusz Pieńkowski Aleksander Bilewicz |
author_facet | Kamil Wawrowicz Agnieszka Majkowska-Pilip Damian Gaweł Ewelina Chajduk Tadeusz Pieńkowski Aleksander Bilewicz |
author_sort | Kamil Wawrowicz |
collection | DOAJ |
description | <sup>193m</sup>Pt and <sup>195m</sup>Pt radionuclides are therapeutically attractive Auger electron emitters with notably high Auger electron yield per decay. The present paper summarizes the first step of research on the applications of core-shell (Au@Pt) nanoparticles for electron Auger therapy of HER2+ (human epidermal growth factor receptor 2) breast cancer and hepatocellular carcinoma. Gold nanoparticles (30 nm) were synthesized covered with a platinum shell at high efficiency (>80%) and were further evaluated for in vitro studies such as binding affinity, internalization and cytotoxicity. To find the mechanism(s) responsible for platinum cytotoxicity in HepG2 cells, the platinum concentration in isolated cell nuclei and cytoplasm was determined using ICP-MS (inductively coupled plasma mass spectrometry). Lack of platinum in cell nuclei suggests that the cytotoxic effect is associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Studies carried out on the SKOV-3 cell line with the use of a synthesized targeting bioconjugate (Au@Pt-PEG-trastuzumab) revealed a high affinity of this preparation to HER2+ cells, its internalization, its placement in the perinuclear area and partial intranuclear location. The specific binding for HER2 negative cells, MDA-MB-231, was negligible and Au@Pt-PEG-trastuzumab did not enter these cells. The results obtained are promising and warrant future investigation of Auger electron therapy using <sup>193m</sup>Pt and <sup>195m</sup>Pt based radiopharmaceuticals. |
first_indexed | 2024-03-10T12:37:40Z |
format | Article |
id | doaj.art-62dc08be548b4761b95df3aeecc6ad16 |
institution | Directory Open Access Journal |
issn | 1420-3049 |
language | English |
last_indexed | 2024-03-10T12:37:40Z |
publishDate | 2021-04-01 |
publisher | MDPI AG |
record_format | Article |
series | Molecules |
spelling | doaj.art-62dc08be548b4761b95df3aeecc6ad162023-11-21T14:06:40ZengMDPI AGMolecules1420-30492021-04-01267205110.3390/molecules26072051Au@Pt Core-Shell Nanoparticle Bioconjugates for the Therapy of HER2+ Breast Cancer and Hepatocellular Carcinoma. Model Studies on the Applicability of <sup>193m</sup>Pt and <sup>195m</sup>Pt Radionuclides in Auger Electron TherapyKamil Wawrowicz0Agnieszka Majkowska-Pilip1Damian Gaweł2Ewelina Chajduk3Tadeusz Pieńkowski4Aleksander Bilewicz5Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16 Str., 03-195 Warsaw, PolandCentre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16 Str., 03-195 Warsaw, PolandDepartment of Immunohematology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, PolandLaboratory of Nuclear Analytical Techniques, Institute of Nuclear Chemistry and Technology, Dorodna 16 Str., 03-195 Warsaw, PolandDepartment of Oncology and Breast Diseases, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, PolandCentre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16 Str., 03-195 Warsaw, Poland<sup>193m</sup>Pt and <sup>195m</sup>Pt radionuclides are therapeutically attractive Auger electron emitters with notably high Auger electron yield per decay. The present paper summarizes the first step of research on the applications of core-shell (Au@Pt) nanoparticles for electron Auger therapy of HER2+ (human epidermal growth factor receptor 2) breast cancer and hepatocellular carcinoma. Gold nanoparticles (30 nm) were synthesized covered with a platinum shell at high efficiency (>80%) and were further evaluated for in vitro studies such as binding affinity, internalization and cytotoxicity. To find the mechanism(s) responsible for platinum cytotoxicity in HepG2 cells, the platinum concentration in isolated cell nuclei and cytoplasm was determined using ICP-MS (inductively coupled plasma mass spectrometry). Lack of platinum in cell nuclei suggests that the cytotoxic effect is associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Studies carried out on the SKOV-3 cell line with the use of a synthesized targeting bioconjugate (Au@Pt-PEG-trastuzumab) revealed a high affinity of this preparation to HER2+ cells, its internalization, its placement in the perinuclear area and partial intranuclear location. The specific binding for HER2 negative cells, MDA-MB-231, was negligible and Au@Pt-PEG-trastuzumab did not enter these cells. The results obtained are promising and warrant future investigation of Auger electron therapy using <sup>193m</sup>Pt and <sup>195m</sup>Pt based radiopharmaceuticals.https://www.mdpi.com/1420-3049/26/7/2051core-shell nanoparticlesplatinumhepatocellular carcinomabreast cancerAuger electron therapy |
spellingShingle | Kamil Wawrowicz Agnieszka Majkowska-Pilip Damian Gaweł Ewelina Chajduk Tadeusz Pieńkowski Aleksander Bilewicz Au@Pt Core-Shell Nanoparticle Bioconjugates for the Therapy of HER2+ Breast Cancer and Hepatocellular Carcinoma. Model Studies on the Applicability of <sup>193m</sup>Pt and <sup>195m</sup>Pt Radionuclides in Auger Electron Therapy Molecules core-shell nanoparticles platinum hepatocellular carcinoma breast cancer Auger electron therapy |
title | Au@Pt Core-Shell Nanoparticle Bioconjugates for the Therapy of HER2+ Breast Cancer and Hepatocellular Carcinoma. Model Studies on the Applicability of <sup>193m</sup>Pt and <sup>195m</sup>Pt Radionuclides in Auger Electron Therapy |
title_full | Au@Pt Core-Shell Nanoparticle Bioconjugates for the Therapy of HER2+ Breast Cancer and Hepatocellular Carcinoma. Model Studies on the Applicability of <sup>193m</sup>Pt and <sup>195m</sup>Pt Radionuclides in Auger Electron Therapy |
title_fullStr | Au@Pt Core-Shell Nanoparticle Bioconjugates for the Therapy of HER2+ Breast Cancer and Hepatocellular Carcinoma. Model Studies on the Applicability of <sup>193m</sup>Pt and <sup>195m</sup>Pt Radionuclides in Auger Electron Therapy |
title_full_unstemmed | Au@Pt Core-Shell Nanoparticle Bioconjugates for the Therapy of HER2+ Breast Cancer and Hepatocellular Carcinoma. Model Studies on the Applicability of <sup>193m</sup>Pt and <sup>195m</sup>Pt Radionuclides in Auger Electron Therapy |
title_short | Au@Pt Core-Shell Nanoparticle Bioconjugates for the Therapy of HER2+ Breast Cancer and Hepatocellular Carcinoma. Model Studies on the Applicability of <sup>193m</sup>Pt and <sup>195m</sup>Pt Radionuclides in Auger Electron Therapy |
title_sort | au pt core shell nanoparticle bioconjugates for the therapy of her2 breast cancer and hepatocellular carcinoma model studies on the applicability of sup 193m sup pt and sup 195m sup pt radionuclides in auger electron therapy |
topic | core-shell nanoparticles platinum hepatocellular carcinoma breast cancer Auger electron therapy |
url | https://www.mdpi.com/1420-3049/26/7/2051 |
work_keys_str_mv | AT kamilwawrowicz auptcoreshellnanoparticlebioconjugatesforthetherapyofher2breastcancerandhepatocellularcarcinomamodelstudiesontheapplicabilityofsup193msupptandsup195msupptradionuclidesinaugerelectrontherapy AT agnieszkamajkowskapilip auptcoreshellnanoparticlebioconjugatesforthetherapyofher2breastcancerandhepatocellularcarcinomamodelstudiesontheapplicabilityofsup193msupptandsup195msupptradionuclidesinaugerelectrontherapy AT damiangaweł auptcoreshellnanoparticlebioconjugatesforthetherapyofher2breastcancerandhepatocellularcarcinomamodelstudiesontheapplicabilityofsup193msupptandsup195msupptradionuclidesinaugerelectrontherapy AT ewelinachajduk auptcoreshellnanoparticlebioconjugatesforthetherapyofher2breastcancerandhepatocellularcarcinomamodelstudiesontheapplicabilityofsup193msupptandsup195msupptradionuclidesinaugerelectrontherapy AT tadeuszpienkowski auptcoreshellnanoparticlebioconjugatesforthetherapyofher2breastcancerandhepatocellularcarcinomamodelstudiesontheapplicabilityofsup193msupptandsup195msupptradionuclidesinaugerelectrontherapy AT aleksanderbilewicz auptcoreshellnanoparticlebioconjugatesforthetherapyofher2breastcancerandhepatocellularcarcinomamodelstudiesontheapplicabilityofsup193msupptandsup195msupptradionuclidesinaugerelectrontherapy |