Synthesis, Characterization, and Therapeutic Efficacy of <sup>177</sup>Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors
As an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanopart...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/7/1943 |
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| author | Dragana Stanković Magdalena Radović Aljoša Stanković Marija Mirković Aleksandar Vukadinović Milica Mijović Zorana Milanović Miloš Ognjanović Drina Janković Bratislav Antić Sanja Vranješ-Đurić Miroslav Savić Željko Prijović |
| author_facet | Dragana Stanković Magdalena Radović Aljoša Stanković Marija Mirković Aleksandar Vukadinović Milica Mijović Zorana Milanović Miloš Ognjanović Drina Janković Bratislav Antić Sanja Vranješ-Đurić Miroslav Savić Željko Prijović |
| author_sort | Dragana Stanković |
| collection | DOAJ |
| description | As an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanoparticles (SPIONs) coated with meso-1,2-dimercaptosuccinic acid (DMSA) and radiolabeled with Lutetium-177 (<sup>177</sup>Lu), generating <sup>177</sup>Lu-DMSA@SPIONs as a potential antitumor agent for nanobrachytherapy. Efficient radiolabeling of DMSA@SPIONS by <sup>177</sup>Lu resulted in a stable bond with minimal leakage in vitro. After an intratumoral injection to mouse colorectal CT-26 or breast 4T1 subcutaneous tumors, the nanoparticles remained well localized at the injection site for weeks, with limited leakage. The dose of 3.70 MBq/100 µg/50 µL of <sup>177</sup>Lu-DMSA@SPIONs applied intratumorally resulted in a high therapeutic efficacy, without signs of general toxicity. A decreased dose of 1.85 MBq/100 µg/50 µL still retained therapeutic efficacy, while an increased dose of 9.25 MBq/100 µg/50 µL did not significantly benefit the therapy. Histopathology analysis revealed that the <sup>177</sup>Lu-DMSA@SPIONs act within a limited range around the injection site, which explains the good therapeutic efficacy achieved by a single administration of a relatively low dose without the need for increased or repeated dosing. Overall, <sup>177</sup>Lu-DMSA@SPIONs are safe and potent agents suitable for intra-tumoral administration for localized tumor radionuclide therapy. |
| first_indexed | 2024-03-11T00:44:16Z |
| format | Article |
| id | doaj.art-c870911185b5459ba73917e3775ea08d |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T00:44:16Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c870911185b5459ba73917e3775ea08d2023-11-18T20:56:00ZengMDPI AGPharmaceutics1999-49232023-07-01157194310.3390/pharmaceutics15071943Synthesis, Characterization, and Therapeutic Efficacy of <sup>177</sup>Lu-DMSA@SPIONs in Nanobrachytherapy of Solid TumorsDragana Stanković0Magdalena Radović1Aljoša Stanković2Marija Mirković3Aleksandar Vukadinović4Milica Mijović5Zorana Milanović6Miloš Ognjanović7Drina Janković8Bratislav Antić9Sanja Vranješ-Đurić10Miroslav Savić11Željko Prijović12Vinča Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaVinča Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaUniversity Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and HerzegovinaVinča Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaVinča Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaFaculty of Medicine, Institute of Pathology, University of Priština in Kosovska Mitrovica, 38220 Kosovska Mitrovica, SerbiaVinča Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaVinča Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaVinča Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaVinča Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaVinča Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaFaculty of Pharmacy, University of Belgrade, 11000 Belgrade, SerbiaVinča Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11001 Belgrade, SerbiaAs an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanoparticles (SPIONs) coated with meso-1,2-dimercaptosuccinic acid (DMSA) and radiolabeled with Lutetium-177 (<sup>177</sup>Lu), generating <sup>177</sup>Lu-DMSA@SPIONs as a potential antitumor agent for nanobrachytherapy. Efficient radiolabeling of DMSA@SPIONS by <sup>177</sup>Lu resulted in a stable bond with minimal leakage in vitro. After an intratumoral injection to mouse colorectal CT-26 or breast 4T1 subcutaneous tumors, the nanoparticles remained well localized at the injection site for weeks, with limited leakage. The dose of 3.70 MBq/100 µg/50 µL of <sup>177</sup>Lu-DMSA@SPIONs applied intratumorally resulted in a high therapeutic efficacy, without signs of general toxicity. A decreased dose of 1.85 MBq/100 µg/50 µL still retained therapeutic efficacy, while an increased dose of 9.25 MBq/100 µg/50 µL did not significantly benefit the therapy. Histopathology analysis revealed that the <sup>177</sup>Lu-DMSA@SPIONs act within a limited range around the injection site, which explains the good therapeutic efficacy achieved by a single administration of a relatively low dose without the need for increased or repeated dosing. Overall, <sup>177</sup>Lu-DMSA@SPIONs are safe and potent agents suitable for intra-tumoral administration for localized tumor radionuclide therapy.https://www.mdpi.com/1999-4923/15/7/1943nanobrachytherapynanoparticles<sup>177</sup>Luradionuclide therapytumor |
| spellingShingle | Dragana Stanković Magdalena Radović Aljoša Stanković Marija Mirković Aleksandar Vukadinović Milica Mijović Zorana Milanović Miloš Ognjanović Drina Janković Bratislav Antić Sanja Vranješ-Đurić Miroslav Savić Željko Prijović Synthesis, Characterization, and Therapeutic Efficacy of <sup>177</sup>Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors Pharmaceutics nanobrachytherapy nanoparticles <sup>177</sup>Lu radionuclide therapy tumor |
| title | Synthesis, Characterization, and Therapeutic Efficacy of <sup>177</sup>Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors |
| title_full | Synthesis, Characterization, and Therapeutic Efficacy of <sup>177</sup>Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors |
| title_fullStr | Synthesis, Characterization, and Therapeutic Efficacy of <sup>177</sup>Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors |
| title_full_unstemmed | Synthesis, Characterization, and Therapeutic Efficacy of <sup>177</sup>Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors |
| title_short | Synthesis, Characterization, and Therapeutic Efficacy of <sup>177</sup>Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors |
| title_sort | synthesis characterization and therapeutic efficacy of sup 177 sup lu dmsa spions in nanobrachytherapy of solid tumors |
| topic | nanobrachytherapy nanoparticles <sup>177</sup>Lu radionuclide therapy tumor |
| url | https://www.mdpi.com/1999-4923/15/7/1943 |
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