Enzyme-instructed supramolecular assemblies promote intracellular boron accumulation for boron neutron capture therapy.

Selective accumulation of boron agents in cancer cells is of critical importance for BNCT. Here we involve enzyme-instructed supramolecular assembly (EISA) to facilitate the accumulation of a typical boron agent borylphenylalanine (BPA) in cancer cells. By covalently conjugating BPA to the phosphorylated assembly precursor, the boron-bearing precursors undergo phosphatase-catalyzed dephosphorylation to yield assembly molecules, which then self-assemble to form nanomaterials. Due to the up-regulated phosphatase activity of cancer cells, kinetic preference allows the EISA to accumulate boron in HeLa cells selectively. Interestingly, by attaching BPA on the backbone or side-chain of precursor, the boron-bearing isomers show different assembly propensity with time-dependent morphology change, which leads to the differentiated accumulation of boron inside cells. Overall, the optimized boron-bearing assembly precursor could significantly improve the boron accumulation compared with BPA in cancer cells. In this study, we have demonstrated a convenient method to introduce boron agents to cancer cells. We envision that the EISA-mediated accumulation of boron will be helpful in the design of boron agents to facilitate BNCT treatment.