TY - JOUR
T1 - Impact of chemical composition on the nanostructure and biological activity of α‑galactosidase‑loaded nanovesicles for Fabry disease treatment
AU - Tomsen-Melero, Judit
AU - Passemard, Solène
AU - García-Aranda, Natalia
AU - Díaz-Riascos, Zamira Vanessa
AU - González-Rioja, Ramon
AU - Pedersen, Jannik Nedergaard
AU - Lyngsø, Jeppe
AU - Merlo-Mas, Josep
AU - Cristóbal-Lecina, Edgar
AU - Corchero, José Luis
AU - Pulido, Daniel
AU - Cámara-Sánchez, Patricia
AU - Portnaya, Irina
AU - Ionita, Inbal
AU - Schwartz, Simó
AU - Veciana, Jaume
AU - Sala, Santi
AU - Royo, Miriam
AU - Córdoba, Alba
AU - Danino, Dganit
AU - Pedersen, Jan Skov
AU - González-Mira, Elisabet
AU - Abasolo, Ibane
AU - Ventosa, Nora
N1 - Publisher Copyright:
© 2021 American Chemical Society
PY - 2021/2/24
Y1 - 2021/2/24
N2 - Fabry disease is a rare lysosomal storage disorder characterized by a deficiency of α-galactosidase A (GLA), a lysosomal hydrolase. The enzyme replacement therapy administering naked GLA shows several drawbacks including poor biodistribution, limited efficacy, and relatively high immunogenicity in Fabry patients. An attractive strategy to overcome these problems is the use of nanocarriers for encapsulating the enzyme. Nanoliposomes functionalized with RGD peptide have already emerged as a good platform to protect and deliver GLA to endothelial cells. However, low colloidal stability and limited enzyme entrapment efficiency could hinder the further pharmaceutical development and the clinical translation of these nanoformulations. Herein, the incorporation of the cationic miristalkonium chloride (MKC) surfactant to RGD nanovesicles is explored, comparing two different nanosystems-quatsomes and hybrid liposomes. In both systems, the positive surface charge introduced by MKC promotes electrostatic interactions between the enzyme and the nanovesicles, improving the loading capacity and colloidal stability. The presence of high MKC content in quatsomes practically abolishes GLA enzymatic activity, while low concentrations of the surfactant in hybrid liposomes stabilize the enzyme without compromising its activity. Moreover, hybrid liposomes show improved efficacy in cell cultures and a good in vitro/ in vivo safety profile, ensuring their future preclinical and clinical development.
AB - Fabry disease is a rare lysosomal storage disorder characterized by a deficiency of α-galactosidase A (GLA), a lysosomal hydrolase. The enzyme replacement therapy administering naked GLA shows several drawbacks including poor biodistribution, limited efficacy, and relatively high immunogenicity in Fabry patients. An attractive strategy to overcome these problems is the use of nanocarriers for encapsulating the enzyme. Nanoliposomes functionalized with RGD peptide have already emerged as a good platform to protect and deliver GLA to endothelial cells. However, low colloidal stability and limited enzyme entrapment efficiency could hinder the further pharmaceutical development and the clinical translation of these nanoformulations. Herein, the incorporation of the cationic miristalkonium chloride (MKC) surfactant to RGD nanovesicles is explored, comparing two different nanosystems-quatsomes and hybrid liposomes. In both systems, the positive surface charge introduced by MKC promotes electrostatic interactions between the enzyme and the nanovesicles, improving the loading capacity and colloidal stability. The presence of high MKC content in quatsomes practically abolishes GLA enzymatic activity, while low concentrations of the surfactant in hybrid liposomes stabilize the enzyme without compromising its activity. Moreover, hybrid liposomes show improved efficacy in cell cultures and a good in vitro/ in vivo safety profile, ensuring their future preclinical and clinical development.
KW - Fabry disease
KW - Miristalkonium chloride (MKC)
KW - Nanovesicles
KW - RGD targeting
KW - α-galactosidase A (GLA)
UR - http://www.scopus.com/inward/record.url?scp=85101512052&partnerID=8YFLogxK
U2 - 10.1021/acsami.0c16871
DO - 10.1021/acsami.0c16871
M3 - 文章
C2 - 33583172
AN - SCOPUS:85101512052
SN - 1944-8244
VL - 13
SP - 7825
EP - 7838
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
IS - 7
ER -