β-Cyclodextrin (β-CD) is being considered a promising therapy for Niemann-Pick C (NPC) disease because of its ability to mobilise the entrapped cholesterol from lysosomes, however, a major limitation is its inability to cross the blood-brain barrier (BBB) and address the central nervous system (CNS) manifestations of the disease. Considering this, we aimed to design nanoparticles able to cross the BBB and deliver β-CD into the CNS lysosomes. The physicochemical characteristics of β-CD-loaded nanoparticles were evaluated by dynamic light scattering, small-angle X-ray scattering, and cryogenic transmission electron microscopy. The in vitro analyses were performed with NPC dermal fibroblasts and the β-CD-loaded nanoparticles were tracked in vivo. The nanoparticles showed a mean diameter around 120 nm with a disordered bicontinuous inner structure. The nanoparticles did not cause decrease in cell viability, impairment in the antioxidant enzymes activity, damage to biomolecules or release of reactive species in NPC dermal fibroblasts; also, they did not induce genotoxicity or alter the mitochondrial function in healthy fibroblasts. The β-CD-loaded nanoparticles were taken up by lysosomes reducing the cholesterol accumulated in NPC fibroblasts and reached the CNS of mice more intensely than other organs, demonstrating advantages compared to the free β-CD. The results demonstrated the potential of the β-CD-loaded nanoparticles in reducing the brain impairment of NPC.

中文翻译：

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含有 β-环糊精的纳米颗粒可用于治疗 Niemann-Pick C。

β-环糊精 (β-CD) 被认为是治疗尼曼-匹克 C (NPC) 病的有希望的疗法，因为它能够从溶酶体中动员截留的胆固醇，但是，一个主要的限制是它无法穿过血脑屏障(BBB) 并解决该疾病的中枢神经系统 (CNS) 表现。考虑到这一点，我们旨在设计能够穿过 BBB 并将 β-CD 输送到 CNS 溶酶体的纳米颗粒。通过动态光散射、小角 X 射线散射和低温透射电子显微镜评估了负载 β-CD 的纳米粒子的理化特性。用 NPC 真皮成纤维细胞进行体外分析，并在体内跟踪加载 β-CD 的纳米颗粒。纳米粒子的平均直径约为 120 nm，具有无序的双连续内部结构。纳米颗粒不会导致细胞活力降低、抗氧化酶活性受损、生物分子损伤或 NPC 真皮成纤维细胞中活性物质的释放；此外，它们不会诱导基因毒性或改变健康成纤维细胞的线粒体功能。载有 β-CD 的纳米颗粒被溶酶体吸收，减少了 NPC 成纤维细胞中积累的胆固醇，并比其他器官更强烈地到达小鼠的中枢神经系统，与游离 β-CD 相比具有优势。结果证明了负载 β-CD 的纳米颗粒在减少 NPC 脑损伤方面的潜力。它们不会诱导基因毒性或改变健康成纤维细胞的线粒体功能。载有 β-CD 的纳米颗粒被溶酶体吸收，减少了 NPC 成纤维细胞中积累的胆固醇，并比其他器官更强烈地到达小鼠的中枢神经系统，与游离 β-CD 相比具有优势。结果证明了负载 β-CD 的纳米颗粒在减少 NPC 脑损伤方面的潜力。它们不会诱导基因毒性或改变健康成纤维细胞的线粒体功能。载有 β-CD 的纳米颗粒被溶酶体吸收，减少了 NPC 成纤维细胞中积累的胆固醇，并比其他器官更强烈地到达小鼠的中枢神经系统，与游离 β-CD 相比具有优势。结果证明了负载 β-CD 的纳米颗粒在减少 NPC 脑损伤方面的潜力。