Boronic acid copolymers for direct loading and acid-triggered release of Bis-T-23 in cultured podocytes

We report an acid-reversible linker for triggered release of Bis-T-23, an experimental small molecule drug for kidney disease treatment that restores podocyte morphology during disease. Bis-T-23 contains catechols, which form an acid-reversible, covalent boronate ester bond with boronic acids. We synthesized phenylboronic acid-containing polymers using reversible addition-fragmentation chain transfer polymerization that were able to directly load and solubilize Bis-T-23. Because of the reversibility of the boronic ester bond, drug was released in its native form in a pH-dependent manner. The polymers rapidly trafficked into acidic compartments and did not exhibit cytotoxicity, and polymer-drug conjugates successfully delivered Bis-T-23 into cultured podocytes.