Polyelectrolyte coated BaTiO₃ nanoparticles for second harmonic generation imaging-guided photodynamic therapy with improved stability and enhanced cellular uptake

Photodynamic therapy (PDT) based on novel nanomaterials has attracted considerable interest in recent years. In this work, we fabricate positively charged polyelectrolyte (PAH) coated barium titanate (BaTiO₃, BT) nanoparticles (BT-PAH) with improved colloidal stability and enhanced cellular uptake efficiency. The BT-PAH nanoparticles are demonstrated to be promising as second harmonic generation (SHG) imaging probes due to their coherent and non-bleaching signals under femtosecond laser excitation, which is useful for long-term monitoring of cell dynamics. Furthermore, Ce6, a type of photosensitizer for PDT, is successfully loaded on BT-PAH to form BT-Ce6-PAH nanocomposites. Enhanced PDT efficiency is achieved due to higher cellular uptake of Ce6 assisted by BT-PAH nanocomposite-loading, which is confirmed by SHG and fluorescence cell imaging. Our work illustrates that BT-PAH nanoparticles can serve as promising contrast agents for SHG imaging and highly efficient nanocarriers for SHG imaging-guided photodynamic therapy.