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Volume 26
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10.3390/ijms26178291
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Inorganic Silica Nanoparticles Increase Lysosomal Biology and Protease Activity

by
Anastasiia O. Syrocheva
1,
Valentina I. Gorbacheva
1,
Vera S. Egorova
1,
Andrey A. Zamyatnin, Jr.
2,3,4,
Alessandro Parodi
1,2 and
Ekaterina P. Kolesova
1,*
1
Research Center for Translational Medicine, Sirius University of Science and Technology, Sochi 354340, Russia
2
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119234, Russia
3
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia
4
Department of Biochemistry, Sechenov First Moscow State Medical University, Moscow 119991, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(17), 8291; https://doi.org/10.3390/ijms26178291 (registering DOI)
Submission received: 11 July 2025 / Revised: 22 August 2025 / Accepted: 26 August 2025 / Published: 26 August 2025
(This article belongs to the Special Issue Nanoparticles in Molecular Pharmaceutics)
Versions Notes

Abstract

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.
Keywords: drug delivery; nanocarriers; mesoporous silica nanoparticles; albumin nanoparticles; lysosomes; cathepsins drug delivery; nanocarriers; mesoporous silica nanoparticles; albumin nanoparticles; lysosomes; cathepsins

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MDPI and ACS Style

Syrocheva, A.O.; Gorbacheva, V.I.; Egorova, V.S.; Zamyatnin, A.A., Jr.; Parodi, A.; Kolesova, E.P. Inorganic Silica Nanoparticles Increase Lysosomal Biology and Protease Activity. Int. J. Mol. Sci. 2025, 26, 8291. https://doi.org/10.3390/ijms26178291

AMA Style

Syrocheva AO, Gorbacheva VI, Egorova VS, Zamyatnin AA Jr., Parodi A, Kolesova EP. Inorganic Silica Nanoparticles Increase Lysosomal Biology and Protease Activity. International Journal of Molecular Sciences. 2025; 26(17):8291. https://doi.org/10.3390/ijms26178291

Chicago/Turabian Style

Syrocheva, Anastasiia O., Valentina I. Gorbacheva, Vera S. Egorova, Andrey A. Zamyatnin, Jr., Alessandro Parodi, and Ekaterina P. Kolesova. 2025. "Inorganic Silica Nanoparticles Increase Lysosomal Biology and Protease Activity" International Journal of Molecular Sciences 26, no. 17: 8291. https://doi.org/10.3390/ijms26178291

APA Style

Syrocheva, A. O., Gorbacheva, V. I., Egorova, V. S., Zamyatnin, A. A., Jr., Parodi, A., & Kolesova, E. P. (2025). Inorganic Silica Nanoparticles Increase Lysosomal Biology and Protease Activity. International Journal of Molecular Sciences, 26(17), 8291. https://doi.org/10.3390/ijms26178291

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