α-Galactosidase delivery using 30Kc19-human serum albumin nanoparticles for effective treatment of Fabry disease

• Published in: Applied microbiology and biotechnology 2016-12, Vol.100 (24), p.10395-10402
• Main Authors: Lee, Hong Jai, Park, Hee Ho, Sohn, Youngsoo, Ryu, Jina, Park, Ju Hyun, Rhee, Won Jong, Park, Tai Hyun
• Format: Article
• Language: English
• Subjects: alpha-Galactosidase - metabolism; Animals; Biomedical and Life Sciences; Biotechnologically Relevant Enzymes and Proteins; Biotechnology; Biotransformation; Bombyx; Bombyx mori; Cells, Cultured; Drug Carriers - metabolism; Enzyme Replacement Therapy - methods; Fabry Disease - therapy; Fibroblasts - metabolism; Humans; Insect Proteins - metabolism; Life Sciences; Microbial Genetics and Genomics; Microbiology; Nanoparticles - metabolism; Nanoparticles - ultrastructure; Serum Albumin - metabolism; Serum Albumin, Human; Trihexosylceramides - metabolism
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-016-7689-z

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.