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Overcoming Endocytosis Deficiency by Cubosome Nanocarriers


Prange, Jenny A; Aleandri, Simone; Komisarski, Marek; Luciani, Alessandro; Käch, Andres; Schuh, Claus-Dieter; Hall, Andrew M; Mezzenga, Raffaele; Devuyst, Olivier; Landau, Ehud M (2019). Overcoming Endocytosis Deficiency by Cubosome Nanocarriers. ACS Applied Bio Materials, 2(6):2490-2499.

Abstract

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.

Abstract

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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
04 Faculty of Medicine > Center for Microscopy and Image Analysis
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Physical Sciences > Biomaterials
Physical Sciences > General Chemistry
Physical Sciences > Biomedical Engineering
Health Sciences > Biochemistry (medical)
Language:English
Date:16 May 2019
Deposited On:16 Jan 2020 09:46
Last Modified:29 Jul 2020 12:43
Publisher:American Chemical Society (ACS)
ISSN:2576-6422
OA Status:Green
Publisher DOI:https://doi.org/10.1021/acsabm.9b00187

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