Syrocheva Anastasiia O, Gorbacheva Valentina I, Egorova Vera S, Zamyatnin Andrey A, Parodi Alessandro, Kolesova Ekaterina P
Research Center for Translational Medicine, Sirius University of Science and Technology, Sochi 354340, Russia.
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119234, Russia.
Int J Mol Sci. 2025 Aug 26;26(17):8291. doi: 10.3390/ijms26178291.
The use of nanoparticles has revolutionized drug delivery by enabling targeted and controlled therapeutic release. However, their interactions with intracellular organelles, particularly lysosomes, are not yet fully understood. This study delineates the differential effects of two widely used nanocarriers-mesoporous silica (MSNs) and albumin (ANPs) nanoparticles-on lysosomal biology, with a focus on the expression and activity of cathepsins (CtsB and CtsD), which are key proteases involved in protein degradation and maintaining cellular balance. These two types of nanoparticles, differing in their material and degradability, exhibit distinct behaviors inside the cell. We demonstrate that inorganic MSNs cause significant changes in lysosomal function by altering lysosomal content and cathepsin levels, without triggering lysosomal membrane permeabilization-a typical response to organic particle stress. In contrast, ANPs-which are susceptible to lysosomal cathepsin degradation-induce milder changes in cathepsin expression and maintain lysosomal integrity. Our results highlight that the composition of nanocarriers plays a pivotal role in modulating lysosomal protease activity and maintaining overall cellular homeostasis, highlighting the importance of these parameters in the rational design of drug delivery platforms.
纳米颗粒的应用通过实现靶向和可控的治疗性释放，彻底改变了药物递送方式。然而，它们与细胞内细胞器，尤其是溶酶体的相互作用尚未完全明晰。本研究阐述了两种广泛使用的纳米载体——介孔二氧化硅（MSNs）和白蛋白（ANPs）纳米颗粒——对溶酶体生物学的不同影响，重点关注组织蛋白酶（CtsB和CtsD）的表达和活性，这些是参与蛋白质降解和维持细胞平衡的关键蛋白酶。这两种纳米颗粒在材料和可降解性方面存在差异，在细胞内表现出不同的行为。我们证明，无机MSNs通过改变溶酶体内容物和组织蛋白酶水平，导致溶酶体功能发生显著变化，而不会引发溶酶体膜通透性增加——这是对有机颗粒应激的典型反应。相比之下，易受溶酶体组织蛋白酶降解的ANPs，会引起组织蛋白酶表达的较轻微变化，并维持溶酶体的完整性。我们的结果强调，纳米载体的组成在调节溶酶体蛋白酶活性和维持整体细胞稳态方面起着关键作用，突出了这些参数在合理设计药物递送平台中的重要性。
