Highly Versatile Polyelectrolyte Complexes for Improving the Enzyme Replacement Therapy of Lysosomal Storage Disorders

Marina I. Giannotti, Ibane Abasolo, Mireia Oliva, Fernanda Andrade, Natalia García-Aranda, Marta Melgarejo, Daniel Pulido, José L. Corchero, Yolanda Fernández, Antonio Villaverde, Miriam Royo, María F. García-Parajo, Fausto Sanz, Simó Schwartz

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)


© 2016 American Chemical Society. Lysosomal storage disorders are currently treated by enzyme replacement therapy (ERT) through the direct administration of the unprotected recombinant protein to the patients. Herein we present an ionically cross-linked polyelectrolyte complex (PEC) composed of trimethyl chitosan (TMC) and α-galactosidase A (GLA), the defective enzyme in Fabry disease, with the capability of directly targeting endothelial cells by incorporating peptide ligands containing the RGD sequence. We assessed the physicochemical properties, cytotoxicity, and hemocompatibility of RGD-targeted and untargeted PECs, the uptake by endothelial cells and the intracellular activity of PECs in cell culture models of Fabry disease. Moreover, we also explored the effect of different freeze-drying procedures in the overall activity of the PECs. Our results indicate that the use of integrin-binding RGD moiety within the PEC increases their uptake and the efficacy of the GLA enzyme, while the freeze-drying allows the activity of the therapeutic protein to remain intact. Overall, these results highlight the potential of TMC-based PECs as a highly versatile and feasible drug delivery system for improving the ERT of lysosomal storage disorders.
Original languageEnglish
Pages (from-to)25741-25752
JournalACS Applied Materials & Interfaces
Publication statusPublished - 5 Oct 2016


  • Fabry disease
  • enzyme replacement therapy
  • lysosomal delivery
  • nanomedicine
  • polyelectrolyte complexes
  • trimethyl chitosan
  • α-galactosidase A

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