Proteolytic Resistance Determines Albumin Nanoparticle Drug Delivery Properties and Increases Cathepsin B, D, and G Expression

Proteolytic activity is pivotal in maintaining cell homeostasis and function. In pathological conditions such as cancer, it covers a key role in tumor cell viability, spreading to distant organs, and response to the treatment. Endosomes represent one of the major sites of cellular proteolytic activi...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-06, Vol.24 (12), p.10245
Main Authors: Kolesova, Ekaterina P, Egorova, Vera S, Syrocheva, Anastasiia O, Frolova, Anastasiia S, Kostyushev, Dmitry, Kostyusheva, Anastasiia, Brezgin, Sergey, Trushina, Daria B, Fatkhutdinova, Landysh, Zyuzin, Mikhail, Demina, Polina A, Khaydukov, Evgeny V, Zamyatnin, Jr, Andrey A, Parodi, Alessandro
Format: Article
Language:English
Subjects:
Albumin
albumin nanoparticles
Albumins - metabolism
biological carriers
Cathepsin B - metabolism
Cathepsin D - metabolism
Cathepsins
drug delivery
Drug delivery systems
Drugs
Evaluation
Humans
lysosomal enzymes
Lysosomes - metabolism
Nanoparticles
Neoplasms - metabolism
Peptide Hydrolases - metabolism
protein degradation
Proteolysis
Vehicles
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Summary:Proteolytic activity is pivotal in maintaining cell homeostasis and function. In pathological conditions such as cancer, it covers a key role in tumor cell viability, spreading to distant organs, and response to the treatment. Endosomes represent one of the major sites of cellular proteolytic activity and very often represent the final destination of internalized nanoformulations. However, little information about nanoparticle impact on the biology of these organelles is available even though they represent the major location of drug release. In this work, we generated albumin nanoparticles with a different resistance to proteolysis by finely tuning the amount of cross-linker used to stabilize the carriers. After careful characterization of the particles and measurement of their degradation in proteolytic conditions, we determined a relationship between their sensitivity to proteases and their drug delivery properties. These phenomena were characterized by an overall increase in the expression of cathepsin proteases regardless of the different sensitivity of the particles to proteolytic degradation.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241210245