Pheophorbide a-loaded casein micelle for in vivo drug delivery and efficient photodynamic therapy

Casein micelle (CM) is a carrier of hydrophobic molecules in breast milk developed by nature. Herein, we evaluated the potential of CM for delivery of hydrophobic pheophorbide a (Pba), a photosensitizer (PS) for in vivo photodynamic therapy (PDT). CM was constructed with casein sodium salt and calcium ions, and Pba was physically loaded into the inner pockets of CM. The resulting CM-Pba was about 220.03 nm in size and showed superior stability without aggregation in aqueous conditions for 4 months. CM-Pba showed fast cellular uptake into SCC7 tumor cells and killed them by photodynamic effects upon laser irradiation. After intravenous injection into SCC7 tumor-bearing mice, CM-Pba showed about 2.0-fold higher tumor accumulation than free Pba. We observed efficient suppression of tumor growth by PDT using CM-Pba after laser irradiation, and there were no significant side effects. The overall results demonstrated that CM could be a potential drug carrier for hydrophobic PS for in vivo PDT.