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血管活性肠肽-2靶向的二氢卟吩e6负载纳米结构脂质载体:推动胶质母细胞瘤的光动力治疗

Chlorin e6-Loaded Nanostructured Lipid Carriers Targeted by Angiopep-2: Advancing Photodynamic Therapy in Glioblastoma.

作者信息

Pucci Carlotta, De Pasquale Daniele, Degl'Innocenti Andrea, Montorsi Margherita, Desii Andrea, Pero Marta, Martinelli Chiara, Bartolucci Martina, Petretto Andrea, Ciofani Gianni

机构信息

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.

出版信息

Adv Healthc Mater. 2025 Jan;14(2):e2402823. doi: 10.1002/adhm.202402823. Epub 2024 Sep 30.

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 ) 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.

摘要

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。

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