Kinetic analysis of boron therapeutics in head and neck cancer cells by complementary bulk ICP-MS and single-cell (scICP-MS) approaches

Boron neutron capture therapy (BNCT) is an emerging approach to radiotherapy. Neutron capture by a boronated (¹⁰B) therapeutic yields high linear energy transfer alpha particles (helium nuclei, ⁴He) and lithium-7 (⁷Li) atoms, eliciting a localised cell kill effect. Current methods to quantify boron in cells either infer from circulatory concentrations and/or often overlook rapid boron pharmacokinetics. By considering both sample preparation requirements and biological boron dynamics, we report two novel approaches to quantify intracellular boron: firstly, rapid in situ tryptic and acidic digestion of treated cells to avoid premature B efflux (LOD ¹⁰B⁺ = 0.2 μg L⁻¹, LOD ¹¹B⁺ = 0.4 μg L⁻¹) with method suitability confirmed by pre- and post-digestion spike recoveries (102.5 ± 0.5% and 103 ± 3% recovery, respectively); secondly, real-time measurement of boron in live cells using single-cell ICP-MS (scICP-MS) revealing real-time monitoring of boron efflux: biological half-life of ca. 6 min. These complementary approaches deliver unprecedented insight into boron influx and efflux and provide essential bioanalytical tools to advance both BNCT therapeutic development and single-cell elemental analysis.