Intratumoral Transforming Boron Nanosensitizers for Amplified Boron Neutron Capture Therapy

Abstract Boron neutron capture therapy (BNCT) is an advanced binary tumor‐cell‐selected heavy‐particle radiotherapy used for treating invasive malignant tumors. However, its clinical applications have been impeded by the rapid metabolism and insufficient tumor‐specific accumulation of boron agents. To tackle this issue, we develop a smart boron nanosensitizer (BATBN) capable of transforming its size in response to cancer biomarker for optimal balance between penetration and retention of boron‐10 for BNCT. BATBN comprises an ultrasmall boron quantum dots (BQD) core (4 nm) conjugated with cell‐penetrating peptides, which facilitates its cellular uptake and deep tumor penetration. In the tumor microenvironment, the tumor biomarker can specifically initiate a self‐condensation reaction of BATBN, leading to the formation of larger‐sized nanoaggregates. Due to such a specific intratumoral transformation, BATBN demonstrates a 2.4‐fold increase in intratumoral boron concentration and a 5.0‐fold increase in tumor retention time compared to the BQDs. Thus, the tumor volume of the BATBNs‐treatment group is 2.7‐fold smaller than that of BQDs in preclinical tumor models after 21 days of neutron irradiation treatment. This study presents a supramolecular strategy to endow BNCT agents with the biomarker‐activated size interconversion, permitting precise and efficient BNCT for cancer treatment.