Design and synthesis of a novel mitochondria-targeted osteosarcoma theranostic agent based on a PIM1 kinase inhibitor.

Osteosarcoma (OS) is the most common malignancy of the skeletal system, with a poor prognosis and high rate of recurrence. Adequate surgical margin and adjuvant chemotherapy improve the overall survival and limb salvage rate of osteosarcoma patients. Previous studies have showed that OS exhibits an increase in the expression of proviral integration site for Moloney murine leukemia virus 1 (PIM1) kinase, and high levels of PIM1 are also associated with poor OS prognosis and metastasis. We exploited the overexpression of proto-oncogenic PIM1 in OS towards the development of a novel near-infrared imaging and targeted therapeutic agent, namely QCAi-Cy7d by conjugating a PIM1 small molecule inhibitor and heptamethine cyanine dye, for simultaneous guiding surgery and chemotherapy. QCAi-Cy7d showed targeted imaging and anticancer activities against OS in vitro and vivo without any obvious toxicity, and its antitumoral activity was much greater than the parent PIMI inhibitor. These results demonstrated the potential of new conjugate of PIM1 inhibitor and near-infrared imaging, supporting structure-based design and development of theranostic agents for precise tumor imaging and targeted treatment. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Xinzeyu Yi, Zhi Cao, Ying Yuan, Wen Li, Xinyue Cui, Zilin Chen, Xiang Hu, Aixi Yu. Design and synthesis of a novel mitochondria-targeted osteosarcoma theranostic agent based on a PIM1 kinase inhibitor. Journal of controlled release : official journal of the Controlled Release Society. 2021 Apr 10;332:434-447

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PMID: 33662457

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