A Proof-of-Concept Study on the Therapeutic Potential of Au Nanoparticles Radiolabeled with the Alpha-Emitter Actinium-225
Actinium-225 (<sup>225</sup>Ac) is receiving increased attention for its application in targeted radionuclide therapy, due to the short range of its emitted alpha particles in conjunction with their high linear energy transfer, which lead to the eradication of tumor cells while sparing n...
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| Format: | Article |
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MDPI AG
2020-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/2/188 |
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| author | Evangelia-Alexandra Salvanou Dimitris Stellas Charalampos Tsoukalas Barbara Mavroidi Maria Paravatou-Petsotas Nikolaos Kalogeropoulos Stavros Xanthopoulos Franck Denat Gautier Laurent Rana Bazzi Stephane Roux Penelope Bouziotis |
| author_facet | Evangelia-Alexandra Salvanou Dimitris Stellas Charalampos Tsoukalas Barbara Mavroidi Maria Paravatou-Petsotas Nikolaos Kalogeropoulos Stavros Xanthopoulos Franck Denat Gautier Laurent Rana Bazzi Stephane Roux Penelope Bouziotis |
| author_sort | Evangelia-Alexandra Salvanou |
| collection | DOAJ |
| description | Actinium-225 (<sup>225</sup>Ac) is receiving increased attention for its application in targeted radionuclide therapy, due to the short range of its emitted alpha particles in conjunction with their high linear energy transfer, which lead to the eradication of tumor cells while sparing neighboring healthy tissue. The objective of our study was the evaluation of a gold nanoparticle radiolabeled with <sup>225</sup>Ac as an injectable radiopharmaceutical form of brachytherapy for local radiation treatment of cancer. Au@TADOTAGA was radiolabeled with <sup>225</sup>Ac at pH 5.6 (30 min at 70 °C), and in vitro stability was evaluated. In vitro cytotoxicity was assessed in U-87 MG cancer cells, and in vivo biodistribution was performed by intravenous and intratumoral administration of [<sup>225</sup>Ac]<sup>225</sup>Ac-Au@TADOTAGA in U-87 MG tumor-bearing mice. A preliminary study to assess therapeutic efficacy of the intratumorally-injected radio-nanomedicine was performed over a period of 22 days, while the necrotic effect on tumors was evaluated by a histopathology study. We have shown that [<sup>225</sup>Ac]<sup>225</sup>Ac-Au@TADOTAGA resulted in the retardation of tumor growth after its intratumoral injection in U87MG tumor-bearing mice, even though very low activities were injected per mouse. This gold nanoparticle radiopharmaceutical could be applied as an unconventional brachytherapy in injectable form for local radiation treatment of cancer. |
| first_indexed | 2024-04-11T22:45:08Z |
| format | Article |
| id | doaj.art-45e6c77ee5aa4facb16b9a3032e9e91f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T22:45:08Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-45e6c77ee5aa4facb16b9a3032e9e91f2022-12-22T03:58:48ZengMDPI AGPharmaceutics1999-49232020-02-0112218810.3390/pharmaceutics12020188pharmaceutics12020188A Proof-of-Concept Study on the Therapeutic Potential of Au Nanoparticles Radiolabeled with the Alpha-Emitter Actinium-225Evangelia-Alexandra Salvanou0Dimitris Stellas1Charalampos Tsoukalas2Barbara Mavroidi3Maria Paravatou-Petsotas4Nikolaos Kalogeropoulos5Stavros Xanthopoulos6Franck Denat7Gautier Laurent8Rana Bazzi9Stephane Roux10Penelope Bouziotis11Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, 15341 Athens, GreeceInstitute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, GreeceInstitute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, 15341 Athens, GreeceInstitute of Biosciences and Applications, National Center for Scientific Research “Demokritos”, 15341 Athens, GreeceInstitute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, 15341 Athens, GreeceA’ Pathology Department, 401 General Military Hospital of Athens, 11525 Athens, GreeceInstitute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, 15341 Athens, GreeceICMUB, UMR 6302 CNRS-UB, Université Bourgogne Franche-Comté, 21000 Dijon, FranceInstitut UTINAM, UMR 6213 CNRS-UBFC, Université Bourgogne Franche-Comté, 25030 Besançon, FranceInstitut UTINAM, UMR 6213 CNRS-UBFC, Université Bourgogne Franche-Comté, 25030 Besançon, FranceInstitut UTINAM, UMR 6213 CNRS-UBFC, Université Bourgogne Franche-Comté, 25030 Besançon, FranceInstitute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research “Demokritos”, 15341 Athens, GreeceActinium-225 (<sup>225</sup>Ac) is receiving increased attention for its application in targeted radionuclide therapy, due to the short range of its emitted alpha particles in conjunction with their high linear energy transfer, which lead to the eradication of tumor cells while sparing neighboring healthy tissue. The objective of our study was the evaluation of a gold nanoparticle radiolabeled with <sup>225</sup>Ac as an injectable radiopharmaceutical form of brachytherapy for local radiation treatment of cancer. Au@TADOTAGA was radiolabeled with <sup>225</sup>Ac at pH 5.6 (30 min at 70 °C), and in vitro stability was evaluated. In vitro cytotoxicity was assessed in U-87 MG cancer cells, and in vivo biodistribution was performed by intravenous and intratumoral administration of [<sup>225</sup>Ac]<sup>225</sup>Ac-Au@TADOTAGA in U-87 MG tumor-bearing mice. A preliminary study to assess therapeutic efficacy of the intratumorally-injected radio-nanomedicine was performed over a period of 22 days, while the necrotic effect on tumors was evaluated by a histopathology study. We have shown that [<sup>225</sup>Ac]<sup>225</sup>Ac-Au@TADOTAGA resulted in the retardation of tumor growth after its intratumoral injection in U87MG tumor-bearing mice, even though very low activities were injected per mouse. This gold nanoparticle radiopharmaceutical could be applied as an unconventional brachytherapy in injectable form for local radiation treatment of cancer.https://www.mdpi.com/1999-4923/12/2/188actinium-225alpha emittersgold nanoparticlesradiolabelingbrachytherapycancer therapy |
| spellingShingle | Evangelia-Alexandra Salvanou Dimitris Stellas Charalampos Tsoukalas Barbara Mavroidi Maria Paravatou-Petsotas Nikolaos Kalogeropoulos Stavros Xanthopoulos Franck Denat Gautier Laurent Rana Bazzi Stephane Roux Penelope Bouziotis A Proof-of-Concept Study on the Therapeutic Potential of Au Nanoparticles Radiolabeled with the Alpha-Emitter Actinium-225 Pharmaceutics actinium-225 alpha emitters gold nanoparticles radiolabeling brachytherapy cancer therapy |
| title | A Proof-of-Concept Study on the Therapeutic Potential of Au Nanoparticles Radiolabeled with the Alpha-Emitter Actinium-225 |
| title_full | A Proof-of-Concept Study on the Therapeutic Potential of Au Nanoparticles Radiolabeled with the Alpha-Emitter Actinium-225 |
| title_fullStr | A Proof-of-Concept Study on the Therapeutic Potential of Au Nanoparticles Radiolabeled with the Alpha-Emitter Actinium-225 |
| title_full_unstemmed | A Proof-of-Concept Study on the Therapeutic Potential of Au Nanoparticles Radiolabeled with the Alpha-Emitter Actinium-225 |
| title_short | A Proof-of-Concept Study on the Therapeutic Potential of Au Nanoparticles Radiolabeled with the Alpha-Emitter Actinium-225 |
| title_sort | proof of concept study on the therapeutic potential of au nanoparticles radiolabeled with the alpha emitter actinium 225 |
| topic | actinium-225 alpha emitters gold nanoparticles radiolabeling brachytherapy cancer therapy |
| url | https://www.mdpi.com/1999-4923/12/2/188 |
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