Overcoming Endocytosis Deficiency by Cubosome Nanocarriers
| Autor: | Ehud M. Landau, Claus-Dieter Schuh, Jenny A. Prange, Olivier Devuyst, Raffaele Mezzenga, Marek Komisarski, Andrew M. Hall, Alessandro Luciani, Simone Aleandri, Andres Käch |
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| Přispěvatelé: | University of Zurich, Devuyst, Olivier |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
10120 Department of Chemistry
biology 10017 Institute of Anatomy Biochemistry (medical) Endocytic cycle 2502 Biomaterials Biomedical Engineering Albumin 2204 Biomedical Engineering 610 Medicine & health 1600 General Chemistry General Chemistry Endocytosis 2704 Biochemistry (medical) In vitro 10052 Institute of Physiology Biomaterials In vivo Biophysics biology.protein 570 Life sciences Nanocarriers Bovine serum albumin 10024 Center for Microscopy and Image Analysis Intracellular |
| DOI: | 10.5167/uzh-179839 |
| Popis: | The use of lipid-based nanoparticles for the delivery of biomacromolecules has attracted considerable attention due to the current interest in protein-based therapeutics. Cubosomes protect the incorporated therapeutics, which are susceptible to degradation by enzymes, thereby improving their bioavailability, and concomitantly enhance cellular uptake. The cubosome nanoparticles presented herein were loaded with bovine serum albumin (BSA) and characterized by small-angle X-ray scattering and dynamic light scattering techniques, while the BSA encapsulation and its release were evaluated in vitro. The ability of this formulation to increase the cellular uptake of albumin by 2-fold was tested on various types of renal tubular cells and confirmed by in vivo renal uptake experiments in mice. The obtained results show that cubosomes are able to deliver BSA inside the cell through distinct uptake and intracellular routing. These data were substantiated, with evidence of a high cubosome-mediated uptake of BSA in Clcn5 knockout mice characterized by defective receptor-mediated endocytosis. The use of cubosomes as a delivery system thus represents a promising approach to overcome the low endocytic uptake in diseased epithelial cells and to treat dysfunctions of the kidney proximal tubule. |
| Databáze: | OpenAIRE |
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