Development of siRNA-loaded chitosan nanoparticles targeting Galectin-1 for the treatment of glioblastoma multiforme via intranasal administration.
Development of siRNA-loaded chitosan nanoparticles targeting Galectin-1 for the treatment of glioblastoma multiforme via intranasal administration.
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DOI：
10.1016/j.jconrel.2016.02.032
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发表时间：
2015-11
期刊：
影响因子：
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通讯作者：
Matthias van Woensel;N. Wauthoz;R. Rosière;V. Mathieu;R. Kiss;F. Lefranc;B. Steelant;E. Dilissen
中科院分区：
文献类型：
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作者：
Matthias van Woensel;N. Wauthoz;R. Rosière;V. Mathieu;R. Kiss;F. Lefranc;B. Steelant;E. Dilissen
半乳糖凝集素-1（Gal-I）是一种天然存在的半乳糖结合凝集素，在多形性胶质母细胞瘤（GBM）中过表达。Gal-1与肿瘤进展相关，并且是肿瘤微环境中的有效免疫抑制剂。为了抑制GBM中的Gal-1，需要达到中枢神经系统肿瘤的有效疗法，其具有有限的全身作用。在这项研究中，我们首次报告了浓缩的壳聚糖纳米颗粒悬浮液可以在鼻内给药后数小时内将小干扰RNA（siRNA）递送到中枢神经系统肿瘤中。这些纳米颗粒能够高比例地复合靶向Gal-1的siRNA，并保护它们免受RNA酶降解。此外，抗Gal-1 siRNA的成功细胞内递送导致小鼠和人GBM细胞中Gal-1的表达降低。序列特异性RNA干扰导致荷瘤小鼠中超过50%的Gal-1减少。这项研究表明，鼻内途径是一种未充分探索的转运途径，用于在GBM治疗中递送靶向Gal-1的基于siRNA的疗法。
Galectin-1 (Gal-1) is a naturally occurring galactose-binding lectin, which is overexpressed in glioblastoma multiforme (GBM). Gal-1 is associated with tumor progression, and is a potent immune suppressor in the tumor micro-environment. To inhibit Gal-1 in GBM, an effective therapy is required that reaches the central nervous system tumor, with limited systemic effects. In this study, we report for the first time that concentrated chitosan nanoparticle suspensions can deliver small interfering RNA (siRNA) into the central nervous system tumor within hours after intranasal administration. These nanoparticles are able to complex siRNA targeting Gal-1 to a high percentage, and protect them from RNAse degradation. Moreover, a successful intracellular delivery of anti-Gal-1 siRNA resulted in a decreased expression of Gal-1 in both murine and human GBM cells. Sequence specific RNAinterference, resulted in more than 50% Gal-1 reduction in tumor bearing mice. This study indicates that the intranasal pathway is an underexplored transport route for delivering siRNA-based therapies targeting Gal-1 in the treatment of GBM.