Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity
| Autor: | Otto C. Boerman, Sandra Heskamp, Uwe Karst, Nicola Margiotta, Michele Iafisco, Michael Brand, Martin Bornhaeuser, Karlijn Codee-van der Schilden, Nandini Asokan, Barbara Crone, Robin A. Nadar, Sander C.G. Leeuwenburgh, Kambiz Farbod, Alessandra Curci, Jeroen J.J.P. van den Beucken, Lukas Schlatt |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Magnetic Resonance Spectroscopy theranostic medicine.medical_treatment lcsh:Medicine Platinum Compounds Pharmacology Mice 0302 clinical medicine Drug Delivery Systems bone-targeting Bone cancer lcsh:Science Zebrafish Multidisciplinary Molecular medicine Diphosphonates Chemistry Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] 030220 oncology & carcinogenesis Drug delivery Toxicity Injections Intravenous Systemic administration chemistry.chemical_element Antineoplastic Agents Bone Neoplasms Calcium Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] Article Bone and Bones 03 medical and health sciences Medical research In vivo medicine Bisphosphonate Animals Radioisotopes Tibia Bone metastases lcsh:R In vitro Mice Inbred C57BL 030104 developmental biology lcsh:Q 195mPlatinum Platinum Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] |
| Zdroj: | Scientific Reports Scientific Reports, 10 Scientific reports (Nature Publishing Group) 10 (2020). doi:10.1038/s41598-020-62039-2 info:cnr-pdr/source/autori:Nadar, Robin A.; Farbod, Kambiz; Codee-van der Schilden, Karlijn; Schlatt, Lukas; Crone, Barbara; Asokan, Nandini; Curci, Alessandra; Brand, Michael; Bornhaeuser, Martin; Iafisco, Michele; Margiotta, Nicola; Karst, Uwe; Heskamp, Sandra; Boerman, Otto C.; van den Beucken, Jeroen J. J. P.; Leeuwenburgh, Sander C. G./titolo:Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity/doi:10.1038%2Fs41598-020-62039-2/rivista:Scientific reports (Nature Publishing Group)/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume:10 Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) |
| ISSN: | 2045-2322 |
| Popis: | Platinum-based chemotherapeutics exhibit excellent antitumor properties. However, these drugs cause severe side effects including toxicity, drug resistance, and lack of tumor selectivity. Tumor-targeted drug delivery has demonstrated great potential to overcome these drawbacks. Herein, we aimed to design radioactive bisphosphonate-functionalized platinum (195mPt-BP) complexes to confirm preferential accumulation of these Pt-based drugs in metabolically active bone. In vitro NMR studies revealed that release of Pt from Pt BP complexes increased with decreasing pH. Upon systemic administration to mice, Pt-BP exhibited a 4.5-fold higher affinity to bone compared to platinum complexes lacking the bone-seeking bisphosphonate moiety. These Pt-BP complexes formed less Pt-DNA adducts compared to bisphosphonate-free platinum complexes, indicating that in vivo release of Pt from Pt-BP complexes proceeded relatively slow. Subsequently, radioactive 195mPt-BP complexes were synthesized using 195mPt(NO3)2(en) as precursor and injected intravenously into mice. Specific accumulation of 195mPt-BP was observed at skeletal sites with high metabolic activity using micro-SPECT/CT imaging. Furthermore, laser ablation-ICP-MS imaging of proximal tibia sections confirmed that 195mPt BP co-localized with calcium in the trabeculae of mice tibia. |
| Databáze: | OpenAIRE |
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