In situ construction of a biotinylated [Cu^II₃(POBio)₂] complex for tumor-targeted chemodynamic therapy

Chemodynamic therapy (CDT) generates cytotoxic hydroxyl radicals (•OH) in tumors via Fenton/Fenton-like reactions using elevated H₂O₂ and acidity. However, its clinical potential is limited by poor tumor selectivity and the difficulty in balancing catalytic metal ion doses with toxicity. In this work, using HPBio (2-Pyridinecarboxaldehyde biotin bis-hydrazide) as the ligand, a biotinylated tri-nuclear copper(II) complex of POBio-Cu₃ has been in-situ synthesized. The solution assemble behavior and in-situ oxidation process has been investigated by time-dependent ESI-MS technology. In the atomically precise POBio-Cu₃, biotin moiety was acting as a cancer-targeting unit and multi-nuclear Cu(II) core as a GSH depletor for augmented CDT effect. POBio-Cu₃ could preferentially accumulate in cancerous Hep-G2 cells, due to the cell discrepancy toward normal WI38 cells. The Cu(II) centers in POBio-Cu₃ were available for consuming glutathione (GSH) and amplifying oxidative stress. Furthermore, the results of in vivo experiments showed that POBio-Cu₃ could remarkably inhibit tumor growth without significant damage to major organs.