Proteomic analysis in morquio a cells treated with immobilized enzymatic replacement therapy on nanostructured lipid systems
Identificadores
Identificadores
URI: http://hdl.handle.net/20.500.11940/15803
PMID: 31540344
DOI: 10.3390/ijms20184610
ISSN: 1661-6596
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Fecha de publicación
2019Título de revista
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Tipo de contenido
Artigo
DeCS
mucopolisacaridosis IV | condroitinsulfatasas | nanoestructuras | adulto joven | humanos | tratamiento de sustitución enzimática | sistemas de liberación de medicamentos | células | adulto | proteómica | lípidos | liposomasMeSH
Adult | Humans | Chondroitinsulfatases | Young Adult | Cells | Drug Delivery Systems | Liposomes | Enzyme Replacement Therapy | Proteomics | Lipids | Nanostructures | Mucopolysaccharidosis IVResumen
Morquio A syndrome, or mucopolysaccharidosis type IVA (MPS IVA), is a lysosomal storage disease due to mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. Systemic skeletal dysplasia and the related clinical features of MPS IVA are due to disruption of cartilage and its extracellular matrix, leading to an imbalance of growth. Enzyme replacement therapy (ERT) with recombinant human GALNS, alpha elosulfase, provides a systemic treatment. However, this therapy has a limited impact on skeletal dysplasia because the infused enzyme cannot penetrate cartilage and bone. Therefore, an alternative therapeutic approach to reach the cartilage is an unmet challenge. We have developed a new drug delivery system based on a nanostructure lipid carrier with the capacity to immobilize enzymes used for ERT and to target the lysosomes. This study aimed to assess the effect of the encapsulated enzyme in this new delivery system, using in vitro proteomic technology. We found a greater internalization of the enzyme carried by nanoparticles inside the cells and an improvement of cellular protein routes previously impaired by the disease, compared with conventional ERT. This is the first qualitative and quantitative proteomic assay that demonstrates the advantages of a new delivery system to improve the MPS IVA ERT.