Pucci Carlotta, De Pasquale Daniele, Degl'Innocenti Andrea, Montorsi Margherita, Desii Andrea, Pero Marta, Martinelli Chiara, Bartolucci Martina, Petretto Andrea, Ciofani Gianni
Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy.
Scuola Superiore Sant'Anna, The BioRobotics Institute, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy.
Adv Healthc Mater. 2025 Jan;14(2):e2402823. doi: 10.1002/adhm.202402823. Epub 2024 Sep 30.
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 ) 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.
胶质母细胞瘤(GBM)是一种极具侵袭性的脑肿瘤,以对标准治疗具有抗性而闻名。尽管手术是主要的治疗选择,但它常常导致切除不完全和高复发率。光动力疗法(PDT)有望成为一种辅助治疗方法,但安全问题以及对高功率激光的需求限制了其广泛应用。本研究通过引入一种新型的PDT方法来应对这些挑战,该方法使用包裹在纳米结构脂质载体(Ang-Ce6-NLCs)中的二氢卟吩e6(Ce6),并通过血管活性肠肽-2肽靶向GBM。值得注意的是,使用660 nm的发光二极管(LED)进行单次5分钟的低功率密度(10 mW/cm²)照射对GBM有效,同时降低了与高功率激光相关的安全风险。封装提高了Ce6在生理环境中的稳定性和性能,而血管活性肠肽-2靶向增强了对GBM细胞的递送,使治疗效果最大化并将脱靶效应最小化。研究结果表明,Ang-Ce6-NLCs介导的PDT可显著降低GBM细胞活力,增加氧化应激,减少肿瘤迁移,并增强细胞凋亡。总体而言,这种治疗方法有潜力作为一种安全有效的术中手段,用于清除手术无法触及的GBM浸润细胞,使用低功率LED光将对周围健康组织的损害降至最低,同时使肿瘤治疗效果最大化。