A deep learning-assisted turn-on fluorescent probe for L-BPA detection with mechanistic insight

Boron neutron capture therapy (BNCT) is a binary cancer treatment strategy that relies on the selective delivery of a ¹⁰B-containing drug followed by thermal neutron irradiation, generating localized high-LET particles that destroy tumor cells. L-BPA is the most recent and currently the only marketed boron carrier; however, its poor tumor retention and low solubility significantly limit therapeutic efficacy. Thus, developing improved L-BPA derivatives, as well as tools for efficient monitoring of L-BPA biodistribution, is critically important. Herein, we report a turn-on fluorescent probe, WF324, which undergoes rapid and selective fluorescence enhancement upon interaction with L-BPA. WF324 exhibits a pronounced fluorescence turn-on response at 578 nm (λex = 488 nm) along with a obvious Stokes shift of 90 nm, the probe displays a rapid response with a half-response time (t₁/₂) of 12 s and reaching a stable plateau within 150 s in aqueous solution and shows excellent selectivity with minimal interference from metal ions. The probe exhibited a good linear response toward L-BPA in the concentration range of 0-6 μM, with a detection limit as low as 80.48 nM. In real samples, the sensor achieved recoveries of 90.40-103.11% with RSDs of 0.78-3.96% for L-BPA detection in human urine. These properties make WF324 a promising tool for sensitive detection and real-time monitoring of L-BPA, offering valuable support for future BNCT research and development.