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Glycogen Synthase Kinase 3β Inhibitor Delivered by Chitosan Nanocapsules Promotes Safe, Fast, and Efficient Activation of Wnt Signaling In Vivo
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2020-03-26 , DOI: 10.1021/acsbiomaterials.9b01820
Alfredo Ambrosone 1 , Laura De Matteis 2, 3 , Inés Serrano-Sevilla 1, 2 , Claudia Tortiglione 4 , Jesús M. De La Fuente 1, 2
Affiliation  

The Wnt-β-catenin signaling is an evolutionarily conserved pathway with a prominent role in different biological processes such as stem cell renewal, cell proliferation, and differentiation. Wnt signaling dysfunctions have been associated with developmental and neurological diseases as well as formation and progression of tumors. Nanomedicine may provide safe and efficient drug delivery systems offering breakthrough innovation in targeting Wnt signaling. The natural polymer chitosan represents an excellent candidate for delivery platforms, showing interesting biophysical properties such as high biocompatibility and mucoadhesive properties. In this study, oily core chitosan nanocapsules were designed with the aim to deliver the Wnt signaling agonist alsterpaullone in the model organism Hydra vulgaris. Chitosan nanocapsules show negligible impact on animal morphology, without affecting the viability. Nile red-loaded nanocapsules reveal fast and efficient intracellular delivery of the fluorescent cargo. Short incubations with alsterpaullone-loaded nanocapsules ensure a more effective activation of Wnt signaling with respect to the same concentrations of the free drug. Altogether, these data provide evidence that chitosan nanocapsules may represent a very promising strategy for future therapies targeting the diseases associated with canonical Wnt signaling.

中文翻译:

壳聚糖纳米胶囊提供的糖原合酶激酶3β抑制剂促进体内Wnt信号的安全,快速和有效激活。

Wnt-β-catenin信号传导是一种进化保守的途径,在不同的生物学过程(如干细胞更新,细胞增殖和分化)中具有重要作用。Wnt信号功能障碍已经与发育和神经疾病以及肿瘤的形成和发展相关。纳米医学可以提供安全有效的药物输送系统,在靶向Wnt信号方面提供突破性的创新。天然聚合物壳聚糖代表了传递平台的极佳候选者,表现出令人感兴趣的生物物理特性,例如高生物相容性和粘膜粘附特性​​。在这项研究中,设计了油性壳聚糖核心纳米胶囊,旨在将Wnt信号激动剂alsterpaullone递送至寻常生物Hydra中。壳聚糖纳米胶囊对动物形态的影响可忽略不计,而不影响其生存能力。尼罗河红载纳米胶囊揭示了荧光货物的快速有效的细胞内传递。与装载了Alsterpaullone的纳米胶囊的短时间孵育可确保相对于相同浓度的游离药物更有效地激活Wnt信号传导。总而言之,这些数据提供了证据,证明壳聚糖纳米胶囊可能代表了针对未来与经典Wnt信号相关疾病的治疗方法。
更新日期:2020-03-26
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