HexA-Enzyme Coated Polymer Nanoparticles for the Development of a Drug-Delivery System in the Treatment of Sandhoff Lysosomal Storage Disease
Lysosomal storage disorders (LSDs) are a set of metabolic diseases caused by mutations in genes that are in charge of the production of lysosomal enzymes, resulting in the buildup of non-degraded substrates and the consequent systemic damage that mainly involves the Central Nervous System (CNS). One...
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MDPI AG
2022-03-01
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| Series: | Journal of Functional Biomaterials |
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| Online Access: | https://www.mdpi.com/2079-4983/13/2/37 |
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| author | Eleonora Calzoni Alessio Cesaretti Nicolò Montegiove Alessandro Di Michele Roberto Maria Pellegrino Carla Emiliani |
| author_facet | Eleonora Calzoni Alessio Cesaretti Nicolò Montegiove Alessandro Di Michele Roberto Maria Pellegrino Carla Emiliani |
| author_sort | Eleonora Calzoni |
| collection | DOAJ |
| description | Lysosomal storage disorders (LSDs) are a set of metabolic diseases caused by mutations in genes that are in charge of the production of lysosomal enzymes, resulting in the buildup of non-degraded substrates and the consequent systemic damage that mainly involves the Central Nervous System (CNS). One of the most widely used and studied treatments is Enzyme Replacement Therapy, which is based on the administration of the recombinant deficient enzyme. This strategy has often proved fallacious due to the enzyme instability in body fluids and its inability to reach adequate levels in the CNS. In this work, we developed a system based on nanotechnology that allows a stable enzyme to be obtained by its covalent immobilization on nanoparticles (NPs) of polylactic acid, subsequently administered to a cellular model of LSDs, i.e., Sandhoff disease, caused by the absence or deficiency of the β-<span style="font-variant: small-caps;">d</span>-<i>N</i>-acetyl-hexosaminidase A (HexA) enzyme. The HexA enzymes, loaded onto the polymeric NPs through an immobilization procedure that has already been investigated and validated, were found to be stable over time, maintain optimal kinetic parameters, be able to permeate the plasma membrane, hydrolyze HexA’s natural substrate, and restore enzyme activity close to the levels of healthy cells. These results thus lay the foundation for testing the HexA-NPs in animal models of the disease and thus obtaining an efficient drug-delivery system. |
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| institution | Directory Open Access Journal |
| issn | 2079-4983 |
| language | English |
| last_indexed | 2024-03-09T23:25:11Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Functional Biomaterials |
| spelling | doaj.art-3a0d43b54ec14c1b9c943155863d6bf32023-11-23T17:19:06ZengMDPI AGJournal of Functional Biomaterials2079-49832022-03-011323710.3390/jfb13020037HexA-Enzyme Coated Polymer Nanoparticles for the Development of a Drug-Delivery System in the Treatment of Sandhoff Lysosomal Storage DiseaseEleonora Calzoni0Alessio Cesaretti1Nicolò Montegiove2Alessandro Di Michele3Roberto Maria Pellegrino4Carla Emiliani5Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06123 Perugia, ItalyDepartment of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06123 Perugia, ItalyDepartment of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06123 Perugia, ItalyDepartment of Physics and Geology, University of Perugia, Via Pascoli, 06123 Perugia, ItalyDepartment of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06123 Perugia, ItalyDepartment of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06123 Perugia, ItalyLysosomal storage disorders (LSDs) are a set of metabolic diseases caused by mutations in genes that are in charge of the production of lysosomal enzymes, resulting in the buildup of non-degraded substrates and the consequent systemic damage that mainly involves the Central Nervous System (CNS). One of the most widely used and studied treatments is Enzyme Replacement Therapy, which is based on the administration of the recombinant deficient enzyme. This strategy has often proved fallacious due to the enzyme instability in body fluids and its inability to reach adequate levels in the CNS. In this work, we developed a system based on nanotechnology that allows a stable enzyme to be obtained by its covalent immobilization on nanoparticles (NPs) of polylactic acid, subsequently administered to a cellular model of LSDs, i.e., Sandhoff disease, caused by the absence or deficiency of the β-<span style="font-variant: small-caps;">d</span>-<i>N</i>-acetyl-hexosaminidase A (HexA) enzyme. The HexA enzymes, loaded onto the polymeric NPs through an immobilization procedure that has already been investigated and validated, were found to be stable over time, maintain optimal kinetic parameters, be able to permeate the plasma membrane, hydrolyze HexA’s natural substrate, and restore enzyme activity close to the levels of healthy cells. These results thus lay the foundation for testing the HexA-NPs in animal models of the disease and thus obtaining an efficient drug-delivery system.https://www.mdpi.com/2079-4983/13/2/37lysosomal storage disorderscovalent immobilizationbiopolymer nanoparticlesenzyme replacement therapyrestored activityganglioside degradation |
| spellingShingle | Eleonora Calzoni Alessio Cesaretti Nicolò Montegiove Alessandro Di Michele Roberto Maria Pellegrino Carla Emiliani HexA-Enzyme Coated Polymer Nanoparticles for the Development of a Drug-Delivery System in the Treatment of Sandhoff Lysosomal Storage Disease Journal of Functional Biomaterials lysosomal storage disorders covalent immobilization biopolymer nanoparticles enzyme replacement therapy restored activity ganglioside degradation |
| title | HexA-Enzyme Coated Polymer Nanoparticles for the Development of a Drug-Delivery System in the Treatment of Sandhoff Lysosomal Storage Disease |
| title_full | HexA-Enzyme Coated Polymer Nanoparticles for the Development of a Drug-Delivery System in the Treatment of Sandhoff Lysosomal Storage Disease |
| title_fullStr | HexA-Enzyme Coated Polymer Nanoparticles for the Development of a Drug-Delivery System in the Treatment of Sandhoff Lysosomal Storage Disease |
| title_full_unstemmed | HexA-Enzyme Coated Polymer Nanoparticles for the Development of a Drug-Delivery System in the Treatment of Sandhoff Lysosomal Storage Disease |
| title_short | HexA-Enzyme Coated Polymer Nanoparticles for the Development of a Drug-Delivery System in the Treatment of Sandhoff Lysosomal Storage Disease |
| title_sort | hexa enzyme coated polymer nanoparticles for the development of a drug delivery system in the treatment of sandhoff lysosomal storage disease |
| topic | lysosomal storage disorders covalent immobilization biopolymer nanoparticles enzyme replacement therapy restored activity ganglioside degradation |
| url | https://www.mdpi.com/2079-4983/13/2/37 |
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