Defect-free graphene enhances enzyme delivery to fibroblasts derived from patients with lysosomal storage disorders
Chen, Yingxian (University of Manchester. Nanomedicine Lab)
Taufiq, Tooba (The University of Manchester)
Zeng, Niting (University of Manchester. Department of Chemistry)
Lozano, Neus (Institut Català de Nanociència i Nanotecnologia)
Karakasidi, Angeliki (University of Manchester. Nanomedicine Lab)
Church, Heather (Manchester Centre for Genomic Medicine)
Jovanovic, Ana (Salford Royal NHS Foundation Trust)
Jones, Simon A. (Manchester Centre for Genomic Medicine)
Panigrahi, Adyasha (University of Manchester. Department of Chemistry)
Larrosa, Igor (University of Manchester. Department of Chemistry)
Kostarelos, Kostas (Institut Català de Nanociència i Nanotecnologia)
Casiraghi, Cinzia (University of Manchester. Department of Chemistry)
Vranic, Sandra (University of Manchester. Nanomedicine Lab)

Date:	2023
Abstract:	Enzyme replacement therapy shows remarkable clinical improvement in treating lysosomal storage disorders. However, this therapeutic approach is hampered by limitations in the delivery of the enzyme to cells and tissues. Therefore, there is an urgent, unmet clinical need to develop new strategies to enhance the enzyme delivery to diseased cells. Graphene-based materials, due to their dimensionality and favourable pattern of interaction with cells, represent a promising platform for the loading and delivery of therapeutic cargo. Herein, the potential use of graphene-based materials, including defect-free graphene with positive or negative surface charge and graphene oxide with different lateral dimensions, was investigated for the delivery of lysosomal enzymes in fibroblasts derived from patients with Mucopolysaccharidosis VI and Pompe disease. We report excellent biocompatibility of all graphene-based materials up to a concentration of 100 μg mL in the cell lines studied. In addition, a noticeable difference in the uptake profile of the materials was observed. Neither type of graphene oxide was taken up by the cells to a significant extent. In contrast, the two types of graphene were efficiently taken up, localizing in the lysosomes. Furthermore, we demonstrate that cationic graphene flakes can be used as carriers for arylsulfatase B enzyme, for the delivery of the lacking enzyme to the lysosomes of Mucopolysaccharidosis VI fibroblasts. Arylsulfatase B complexed with cationic graphene flakes not only retained the enzymatic activity, but also exerted biological effects almost twice as high as arylsulfatase B alone in the clearance of the substrate in Mucopolysaccharidosis VI fibroblasts. This study lays the groundwork for the potential use of graphene-based materials as carriers for enzyme replacement therapy in lysosomal storage disorders.
Grants:	European Commission 785219 Agencia Estatal de Investigación SEV-2017-0706
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Arylsulfatase ; Cationics ; Defect-free ; Enzyme delivery ; Enzyme replacement therapy ; Graphene oxides ; Lateral dimension ; Lysosomal storage disorder ; Negative surface charges ; Positive surface charge ; Fibroblasts ; Graphite ; Humans ; Lysosomes ; Mucopolysaccharidosis VI ; N-Acetylgalactosamine-4-Sulfatase
Published in:	Nanoscale, Vol. 15, Issue 21 (June 2023) , p. 9348-9364, ISSN 2040-3372

DOI: 10.1039/d2nr04971f

17 p, 7.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > Catalan Institute of Nanoscience and Nanotechnology (ICN2)
Articles > Research articles
Articles > Published articles