Together with a multidisciplinary consortium of Dutch and Italian scientists, Sander Leeuwenburgh and his former Radboudumc colleague Robin Nadar, theme Reconstructive and regenerative medicine, recently reported that radioactive platinum-based anticancer drugs effectively kill cancer cells in bone tumors.
Platinum-based chemotherapeutics such as cisplatin 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. Previously, the researchers of this consortium showed in Scientific Reports that radioactive bisphosphonate-functionalized platinum (195mPt-BP) anticancer drugs preferentially accumulate in metabolically active bone. 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.
Last week a follow-up article from the same consortium in Materials Today Bio revealed that these radioactive platinum-based drugs are effectively targeted to bone tumors. Systemically administered 195mPt-BP drugs accumulate up to seven times more effectively in bone tumors compared to radioactive cisplatin lacking these bone-targeting bisphosphonate ligands. Moreover, these drugs effectively kill cancer cells in bone tumors by local emission of Auger electrons. This radiotherapeutic activity of 195mPt-BP drugs was evidenced by a considerably enhanced DNA damage and apoptosis of metastatic tumor cells as compared to non-radioactive Pt-BP controls. These results provide the first preclinical evidence for specific accumulation and radiotherapeutic activity of theranostic 195mPt-BP drugs, which might open up new avenues of research on treatment of bone metastatic lesions using bone-targeted Auger therapy.
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