Tumor Redox-Responsive Minimalist B/Fe Nano-Chains for Chemodynamically Enhanced Ferroptosis and Synergistic Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) as a binary targeted particle radiotherapy strategy has shown potent anti-cancer potential. However, biological barriers and restricted blood supply pose challenges in achieving adequate boron concentration within deep-seated tumor lesions. BNCT with other anti-cancer therapies, such as X-ray radiotherapy and photothermal therapy, is devised to address the limitations of BNCT efficiency. However, the potential risk of organ-accumulating toxicity and treatment complexity of dual exogenous activation hinders its development. To address this problem, newly redox-responsive boron nano-chains (RBNC) are reported that combine BNCT and endogenous chemodynamic therapy (CDT)-enhanced ferroptosis. RBNC specifically activates nanoparticle size conversion (large-to-small) in response to GSH/H₂O₂ in the tumor microenvironment, releasing boron delivery agents boron quantum dots (BQD) and Fe³⁺. RBNC exhibits negligible systemic toxicity while demonstrating high boron accumulation at tumor. Meanwhile, the introduction of Fe³⁺ not only produces ·OH through reaction with H₂O₂, but also depletes GSH and reduces GPX4 activity in tumors, resulting in amplified intracellular oxidative stress and chemodynamically enhanced ferroptosis. Thus, the work provides a strategy to solve the problem of insufficient boron concentration and poor targeting of boron delivery agents and fill the gaps of BNCT combined with CDT and ferroptosis.