Chlorin e6‐Loaded Nanostructured Lipid Carriers Targeted by Angiopep‐2: Advancing Photodynamic Therapy in Glioblastoma
Carlotta Pucci, Daniele De Pasquale, Andrea Degl’Innocenti, Margherita Montorsi, Andrea Desii, Marta Pero, Chiara Martinelli, Martina Bartolucci, Andrea Petretto, Gianni Ciofani
Abstract
Abstract Glioblastoma (GBM) is a highly aggressive brain tumor known for its resistance to standard treatments. Despite surgery being a primary option, it often leads to incomplete removal and high recurrence rates. Photodynamic therapy (PDT) holds promise as an adjunctive treatment, but safety concerns and the need for high‐power lasers have limited its widespread use. This research addresses these challenges by introducing a novel PDT approach, using chlorin e6 (Ce6) enclosed in nanostructured lipid carriers (Ang‐Ce6‐NLCs) and targeted to GBM with the angiopep‐2 peptide. Remarkably, a single 5‐min irradiation session with LEDs at 660 nm and low power density (10 mW cm − 2 ) proves effective against GBM, while reducing safety risks associated with high‐power lasers. Encapsulation improves Ce6 stability and performance in physiological environments, while angiopep‐2 targeting enhances delivery to GBM cells, maximizing treatment efficacy and minimizing off‐target effects. The findings demonstrate that Ang‐Ce6‐NLCs‐mediated PDT brings about a significant reduction in GBM cell viability, increases oxidative stress, reduces tumor migration, and enhances apoptosis. Overall, such treatment holds potential as a safe and efficient intraoperative removal of GBM infiltrating cells that cannot be reached by surgery, using low‐power LED light to minimize harm to surrounding healthy tissue while maximizing tumor treatment.