Development of Berberine-Loaded Nanoparticles for Astrocytoma Cells Administration and Photodynamic Therapy Stimulation

ABSTRACT Berberine (BBR) is an alkaloid extract from Berberis plants with known anti-inflammatory, antioxidant and antitumor properties, and recently has drawn attention for application also in medical field as photosensitizer in photodynamic therapy. In this study, two BBR hydrophobic salts, namely dodecyl sulfate (S) and laurate (L) were encapsulated in PLGA-based nanoparticles (NPs), coated with chitosan oleate and further functionalized with folic acid. All the BBR-loaded NPs showed to be efficiently internalized into T98G GBM established cells. Although the folic acid increased the internalization, the highest mitochondrial colocalization percentage was reached with NPs BBR-S without folic acid, and collectively the BBR-S appeared as the most successful in cytotoxicity induction. These NPs were then selected to assess the effects of photodynamic therapy toward T98G cells. The results showed that PDT potentiated the viability reduction for the NPs BBR-S at all the administered concentrations, and a 50% reduction of viability was achieved without any cytotoxic side effects on normal rat primary astrocytes. In T98G cells, early and late apoptotic events increased associated with BBR- NPs administration, and a substantial further increase in cell death was recorded following the PDT scheme. Moreover, internalization of NPs BBR-S in combination with PDT, triggered a significant mitochondrial depolarization compared to untreated cells and PDT-only treated cells. In conclusion, the coupling treatment of NPs-BBR with photoactivation approaches resulted successful for inducing favorable cytotoxic effects in GBM established cells.

Sviluppo di Nanoparticelle cariche di Berberina per il trattamento di Astrocitomi e Stimolazione con Terapia Fotodinamica