Academic Journal
Bone tumor–targeted delivery of theranostic 195mPt-bisphosphonate complexes promotes killing of metastatic tumor cells
| العنوان: | Bone tumor–targeted delivery of theranostic 195mPt-bisphosphonate complexes promotes killing of metastatic tumor cells |
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| المؤلفون: | Nadar, R. A., Franssen, G. M., Van Dijk, N. W. M., Codee-van der Schilden, K., de Weijert, M., Oosterwijk, E., Iafisco, M., Margiotta, N., Heskamp, S., van den Beucken, J. J. J. P., Leeuwenburgh, S. C. G. |
| المساهمون: | Nadar, R. A., Franssen, G. M., Van Dijk, N. W. M., Codee-van der Schilden, K., de Weijert, M., Oosterwijk, E., Iafisco, M., Margiotta, N., Heskamp, S., van den Beucken, J. J. J. P., Leeuwenburgh, S. C. G. |
| سنة النشر: | 2021 |
| المجموعة: | Università degli Studi di Bari Aldo Moro: CINECA IRIS |
| مصطلحات موضوعية: | 195m-platinum, Bone-targeting, Bone metastase, Auger therapy, Theranostics |
| الوصف: | Platinum-based drugs such as cisplatin are very potent chemotherapeutics, whereas radioactive platinum (195mPt) is a rich source of low-energy Auger electrons, which kills tumor cells by damaging DNA. Auger electrons damage cells over a very short range. Consequently, 195mPt-based radiopharmaceuticals should be targeted toward tumors to maximize radiotherapeutic efficacy and minimize Pt-based systemic toxicity. Herein, we show that systemically administered radioactive bisphosphonate-functionalized platinum (195mPt-BP) complexes specifically accumulate in intratibial bone metastatic lesions in mice. The 195mPt-BP complexes accumulate 7.3-fold more effectively in bone 7 days after systemic delivery compared to 195mPt-cisplatin lacking bone-targeting bisphosphonate ligands. Therapeutically, 195mPt-BP treatment causes 4.5-fold more γ-H2AX formation, a biomarker for DNA damage in metastatic tumor cells compared to 195mPt-cisplatin. We show that systemically administered 195mPt-BP is radiotherapeutically active, as evidenced by an 11-fold increased DNA damage in metastatic tumor cells compared to non-radioactive Pt-BP controls. Moreover, apoptosis in metastatic tumor cells is enhanced more than 3.4-fold upon systemic administration of 195mPt-BP vs. radioactive 195mPt-cisplatin or non-radioactive Pt-BP controls. These results provide the first preclinical evidence for specific accumulation and strong radiotherapeutic activity of 195mPt-BP in bone metastatic lesions, which offers new avenues of research on radiotherapeutic killing of tumor cells in bone metastases by Auger electrons. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/wos/WOS:000627056400001; volume:9; firstpage:100088; journal:MATERIALS TODAY BIO; https://hdl.handle.net/11586/351677 |
| DOI: | 10.1016/j.mtbio.2020.100088 |
| الاتاحة: | https://hdl.handle.net/11586/351677 https://doi.org/10.1016/j.mtbio.2020.100088 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.AD42702F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.mtbio.2020.100088 |
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