Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, Herestraat 49, Leuven 3000, Belgium; Laboratory of Pharmaceutics and Biopharmaceutics, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Bvd du triomphe CP207, Brussels 1050, Belgium.
Laboratory of Pharmaceutics and Biopharmaceutics, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), Bvd du triomphe CP207, Brussels 1050, Belgium.
J Control Release. 2016 Apr 10;227:71-81. doi: 10.1016/j.jconrel.2016.02.032. Epub 2016 Feb 21.
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.
半乳糖凝集素-1（Gal-1）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 与肿瘤进展有关，是肿瘤微环境中的一种强效免疫抑制剂。为了抑制 GBM 中的 Gal-1，需要一种有效的治疗方法，该方法能够到达中枢神经系统肿瘤，而对全身的影响有限。在这项研究中，我们首次报道，经鼻内给药后数小时内，浓缩壳聚糖纳米颗粒悬浮液即可将小干扰 RNA（siRNA）递送至中枢神经系统肿瘤。这些纳米颗粒能够将靶向 Gal-1 的 siRNA 高效地复合，并保护它们免受 RNAse 降解。此外，抗 Gal-1 siRNA 的成功细胞内递送至鼠和人 GBM 细胞中的 Gal-1 表达降低。序列特异性 RNA 干扰导致肿瘤荷瘤小鼠的 Gal-1 减少超过 50%。这项研究表明，经鼻途径是一种尚未充分探索的输送途径，可用于将针对 Gal-1 的基于 siRNA 的疗法递送至 GBM 的治疗中。
