Towards New Delivery Agents for Boron Neutron Capture Therapy: Synthesis and In Vitro Evaluation of a Set of Fluorinated Carbohydrate Derivatives

硼中子俘获疗法的新型运载剂:一组氟化碳水化合物衍生物的合成及体外评估

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作者:Jelena Matović, Juulia Järvinen, Iris K Sokka, Surachet Imlimthan, Olli Aitio, Mirkka Sarparanta, Jarkko Rautio, Filip S Ekholm

Abstract

Boron Neutron Capture Therapy (BNCT) is a cancer treatment which combines tumor-selective boron delivery agents with thermal neutrons in order to selectively eradicate cancer cells. In this work, we focus on the early-stage development of carbohydrate delivery agents for BNCT. In more detail, we expand upon our previous GLUT-targeting approach by synthesizing and evaluating the potential embedded in a representative set of fluorinated carbohydrates bearing a boron cluster. Our findings indicate that these species may have advantages over the boron delivery agents in current clinical use, e.g., significantly improved boron delivery capacity at the cellular level. Simultaneously, the carbohydrate delivery agents were found to bind strongly to plasma proteins, which may be a concern requiring further action before progression to in vivo studies. Altogether, this work brings new insights into factors which need to be accounted for if attempting to develop theranostic agents for BNCT based on carbohydrates in the future.

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