Size-Tunable Boron Nanoreactors for Boron Neutron Capture Synergistic Chemodynamic Therapy of Tumor

Boron neutron capture therapy (BNCT) stands out as a noninvasive potential modality for invasive malignant tumors, with boron drugs playing a crucial role in its efficacy. Nevertheless, the development of boron drugs with biodegradability, as well as high permeability and retention effects, continues to present significant challenges. Here, we fabricate a size-tunable boron nanoreactor (TBNR) via assembling boron nitride quantum dots (BNQDs) and Fe3+ for tumor BNCT and chemodynamic (CDT) synergistic treatment. The obtained TBNR with an appropriate size exhibits superior tumor accumulation and retention. Upon stimulation by the tumor microenvironment (TME), the contained Fe3+ undergo redox reactions with glutathione (GSH) to produce Fe2+ Fenton reagents, which in turn activate CDT function and simultaneously induce TBNR depolymerization. Subsequently, the released ultrasmall BNQDs exhibit intra-deep penetration characteristic and are fully enriched at the tumor site. The in vivo experiments reveal that TBNR possesses excellent biocompatibility and superior synergistic anti-tumor ability post neutron irradiation, resulting in significant shrinkage of subcutaneous 4T1 tumors. Moreover, the TBNR-mediated BNCT has triggered an obvious immune response, which contributes to the long-term suppression of tumors after neutron irradiation. To conclude, this study provides a new approach for constructing more efficient versatile nanocarriers for BNCT-induced combination cancer therapies.