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多形性胶质母细胞瘤:用于改善抗癌治疗的选择性纳米药物

Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments.

作者信息

Duskey Jason Thomas, Rinaldi Arianna, Ottonelli Ilaria, Caraffi Riccardo, De Benedictis Chiara Alessia, Sauer Ann Katrin, Tosi Giovanni, Vandelli Maria Angela, Ruozi Barbara, Grabrucker Andreas Martin

机构信息

Nanotech Lab, Te.Far.T.I., Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.

Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41125 Modena, Italy.

出版信息

Pharmaceutics. 2022 Jul 12;14(7):1450. doi: 10.3390/pharmaceutics14071450.

Abstract

Glioblastoma Multiforme (GBM) is a devastating disease with a low survival rate and few efficacious treatment options. The fast growth, late diagnostics, and off-target toxicity of currently used drugs represent major barriers that need to be overcome to provide a viable cure. Nanomedicines (NMeds) offer a way to overcome these pitfalls by protecting and loading drugs, increasing blood half-life, and being targetable with specific ligands on their surface. In this study, the FDA-approved polymer poly (lactic-co-glycolic) acid was used to optimise NMeds that were surface modified with a series of potential GBM-specific ligands. The NMeds were fully characterised for their physical and chemical properties, and then in vitro testing was performed to evaluate cell uptake and GBM cell specificity. While all targeted NMeds showed improved uptake, only those decorated with the-cell surface vimentin antibody M08 showed specificity for GBM over healthy cells. Finally, the most promising targeted NMed candidate was loaded with the well-known chemotherapeutic, paclitaxel, to confirm targeting and therapeutic effects in C6 GBM cells. These results demonstrate the importance of using well-optimised NMeds targeted with novel ligands to advance delivery and pharmaceutical effects against diseased cells while minimising the risk for nearby healthy cells.

摘要

多形性胶质母细胞瘤(GBM)是一种致命疾病,生存率低且有效治疗选择有限。目前使用的药物生长迅速、诊断较晚且存在脱靶毒性,这些都是提供可行治疗方法时需要克服的主要障碍。纳米药物(NMeds)通过保护和装载药物、延长血液半衰期以及利用其表面的特定配体实现靶向性,提供了一种克服这些缺陷的方法。在本研究中,使用了美国食品药品监督管理局(FDA)批准的聚合物聚乳酸-乙醇酸来优化纳米药物,这些纳米药物用一系列潜在的GBM特异性配体进行了表面修饰。对纳米药物的物理和化学性质进行了全面表征,然后进行体外测试以评估细胞摄取和GBM细胞特异性。虽然所有靶向纳米药物的摄取都有所改善,但只有那些用细胞表面波形蛋白抗体M08修饰的纳米药物对GBM细胞比对健康细胞表现出特异性。最后,将最有前景的靶向纳米药物候选物装载著名的化疗药物紫杉醇,以确认在C6 GBM细胞中的靶向和治疗效果。这些结果证明了使用经过良好优化的、以新型配体为靶向的纳米药物来推进对病变细胞的递送和药物作用,同时将对附近健康细胞的风险降至最低的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1824/9325049/5d2ed63f8260/pharmaceutics-14-01450-g001.jpg

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