title: α-Galactosidase delivery using 30Kc19-human serum albumin nanoparticles for effective treatment of Fabry disease.
abstract: Fabry disease is a genetic lysosomal storage disease caused by deficiency of α-galactosidase, the enzyme-degrading neutral glycosphingolipid that is transported to lysosome. Glycosphingolipid accumulation by this disease causes multi-organ dysfunction and premature death of the patient. Currently, enzyme replacement therapy (ERT) using recombinant α-galactosidase is the only treatment available for Fabry disease. To maximize the efficacy of treatment, enhancement of cellular delivery and enzyme stability is a challenge in ERT using α-galactosidase. In this study, protein nanoparticles using human serum albumin (HSA) and 30Kc19 protein, originating from silkworm, were used to enhance the delivery and intracellular α-galactosidase stability. 30Kc19-HSA nanoparticles loaded with the α-galactosidase were formed by desolvation method. 30Kc19-HSA nanoparticles had a uniform spherical shape and were well dispersed in cell culture media. 30Kc19-HSA nanoparticles had negligible toxicity to human cells. The nanoparticles exhibited enhanced cellular uptake and intracellular stability of delivered α-galactosidase in human foreskin fibroblast. Additionally, they showed enhanced globotriaosylceramide degradation in Fabry patients' fibroblasts. It is expected that 30Kc19-HSA protein nanoparticles could be used as an effective tool for efficient delivery and enhanced stability of drugs.
authors.affiliation: The School of Chemical and Biological Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea.
authors.forename: Hong Jai
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: The School of Chemical and Biological Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea.
authors.forename: Hee Ho
authors.initials: HH
authors.lastname: Park
authors.affiliation: Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Sohn
authors.affiliation: Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jina
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Department of Medical Biomaterials Engineering, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Division of Bioengineering, Incheon National University, Academy-ro, Yeonsu-gu, Incheon, 406-772, Republic of Korea.
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Rhee
authors.affiliation: The School of Chemical and Biological Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea. thpark@snu.ac.kr.|Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, Republic of Korea. thpark@snu.ac.kr.|Advanced Institutes of Convergence Technology, Suwon, Republic of Korea. thpark@snu.ac.kr.
authors.forename: Tai Hyun
authors.initials: TH
authors.lastname: Park
mesh_terms: D000818:Animals; D001711:Biotransformation; D012831:Bombyx; D002478:Cells, Cultured; D004337:Drug Carriers / Q000378:metabolism*; D056947:Enzyme Replacement Therapy / Q000379:methods*; D000795:Fabry Disease / Q000628:therapy*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism; D053758:Nanoparticles / Q000378:metabolism* / Q000648:ultrastructure; D012709:Serum Albumin / Q000378:metabolism*; D000075462:Serum Albumin, Human; D014281:Trihexosylceramides / Q000378:metabolism; D000519:alpha-Galactosidase / Q000378:metabolism*
chemical_list: C422455:ALB protein, human; D004337:Drug Carriers; D019476:Insect Proteins; D012709:Serum Albumin; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase; D000075462:Serum Albumin, Human
keywords: Drug delivery; Enzyme replacement therapy; Enzyme stability; Fabry disease; Protein nanoparticle