α‐Galactosidase‐A Loaded‐Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration

Abstract

Lysosomal storage disorders (LSD) are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of macromolecules, such as lipids, glycoproteins, and mucopolysaccharides. For instance, the lack of α-galactosidase A (GLA) activity in Fabry disease patients causes the accumulation of glycosphingolipids in the vasculature leading to multiple organ pathology. Enzyme replacement therapy, which is the most common treatment of LSD, exhibits several drawbacks mainly related to the instability and low efficacy of the exogenously administered therapeutic enzyme. In this work, the unprecedented increased enzymatic activity and intracellular penetration achieved by the association of a human recombinant GLA to nanoliposomes functionalized with Arginine-Glycine-Aspartic acid (RGD) peptides is reported. Moreover, these new GLA loaded nanoliposomes lead to a higher efficacy in the reduction of the GLA substrate named globotriasylceramide in a cellular model of Fabry disease, than that achieved by the same concentration of the free enzyme. The preparation of these new liposomal formulations by DELOS-SUSP, based on the depressurization of a CO2 -expanded liquid organic solution, shows the great potential of this CO2 -based methodology for the one-step production of protein-nanoliposome conjugates as bioactive nanomaterials with therapeutic interest.

Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives

“…PEG also provided improvement by increasing enzyme delivery and activity [398]. In the last decade, modification of liposomes with RGD peptides or lysosomotrophic agents has also shown promise, such as the case for α–galactosidase delivery by RGD-functionalized liposomes, or VPRIV®-loaded liposomes targeted by octadecyl-rhodamine B for Gaucher disease [399–402]. …”

Highly Stable and Red‐Emitting Nanovesicles Incorporating Lipophilic Diketopyrrolopyrroles for Cell Imaging

“…26,27 Such structures have recently been studied by some of us as alternative nanocarriers to liposomes, thanks to their outstanding stability and capability of multifunctional activity. [28][29][30] Moreover, we have also recently demonstrated that extremely stable and bright fluorescent organic nanoparticles (FONs) for bioimaging can be obtained by incorporating hydrophobic fluorenyl-derived fluorophores within QS-membranes. 31 In these studies, it was shown that, upon incorporation in QSs, the fluorophores could be stably dispersed in water reducing the ACQ effect.…”

Specific Ion Effects in Cholesterol Monolayers

“…CHOL affects cellular processes by interacting with other membrane lipids and specific proteins, and also participates in several membrane trafficking and transmembrane signaling processes [6,7]. Outside the field of fundamental biology, CHOL is an important element in the development of new biomaterials; as a helper lipid in liposomes developed for drug delivery [8,9] or in lipoplexes for gene therapy [10,11]. It is also an integral ingredient of new surfactant-based highly stable vesicles [12].…”