内吞作用
胰岛素
化学
细胞外
细胞内
背景(考古学)
内吞循环
细胞生物学
葡萄糖摄取
小泡
生物物理学
药物输送
生物化学
药理学
细胞
膜
生物
内分泌学
古生物学
有机化学
作者
Angela Costagliola di Polidoro,Zahra Baghbantarghdari,Vincenza De Gregorio,Simona Silvestri,Paolo A. Netti,Enza Torino
出处
期刊:Biomacromolecules
[American Chemical Society]
日期:2023-04-06
卷期号:24 (5): 2203-2212
被引量:1
标识
DOI:10.1021/acs.biomac.3c00102
摘要
In this work, we compare the role of two different uptake mechanisms in the effectiveness of a nanoformulated drug, specifically insulin. Insulin is activated by interacting with insulin receptors exposed on the liver cell membrane that triggers the uptake and storage of glucose. To prove that the uptake mechanism of a delivery system can interfere directly with the effectiveness of the delivered drug, two extremely different delivery systems are tested. In detail, hydrogel-based NPs (cHANPs) and natural lipid vesicles (EVs) encapsulating insulin are used to trigger the activation of this hormone in 3D liver microtissues (μTs) based on their different uptake mechanisms. Results demonstrated that the fusion mechanism of Ins-EVs mediates faster and more pronounced insulin activation with respect to the endocytic mechanism of Ins-cHANPs. Indeed, the fusion causes an increased reduction in glucose concentration in the culture medium EV-treated l-μTs with respect to free insulin-treated tissues. The same effect is not observed for Ins-cHANPs that, taken up by endocytosis, can only equal the reduction in glucose concentration produced by free insulin in 48 h. Overall, these results demonstrate that the effectiveness of nanoformulated drugs depends on the identity they acquire in the biological context (biological identity). Indeed, the nanoparticle (NP) biological identity, such as the uptake mechanism, triggers a unique set of nano-bio-interactions that is ultimately responsible for their fate both in the extracellular and intracellular compartments.
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