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.
Bioactive materials for therapy and diagnosis
Impact of Chemical Composition on the Nanostructure and Biological Activity of α-Galactosidase-Loaded Nanovesicles for Fabry Disease Treatment
Judit Tomsen-Melero, Solène Passemard, Natalia García-Aranda, Zamira Vanessa Díaz-Riascos, Ramon González-Rioja, Jannik Nedergaard Pedersen, Jeppe Lyngsø, Josep Merlo-Mas, Edgar Cristóbal-Lecina, José Luis Corchero, Daniel Pulido, Patricia Cámara-Sánchez, Irina Portnaya, Inbal Ionita, Simó Schwartz Jr., Jaume Veciana, Santi Sala, Miriam Royo, Alba Córdoba, Dganit Danino, Jan Skov Pedersen, Elisabet González-Mira*, Ibane Abasolo*, and Nora Ventosa*
This paper describes the transition from the normal to inverted Marcus region in solid-state tunnel junctions consisting of self-assembled monolayers of benzotetrathiafulvalene (BTTF), and how this transition determines the performance of a molecular diode. Temperature-dependent normalized differential conductance analyses indicate the participation of the HOMO (highest occupied molecular orbital) at large negative bias, which follows typical thermally activated hopping behavior associated with the normal Marcus regime.
Four novel transition metal-carborane photosensitisers were prepared by Sonogashira cross-coupling of 1-(4-ethynylbenzyl)-2-methyl-o-carborane (A-CB) with halogenated Ru(II)- or Ir(III)-phenanthroline complexes. The resulting boron-rich complexes with one (RuCB and IrCB) or two carborane cages (RuCB2 and IrCB2) were spectroscopically characterised, and their photophysical properties investigated. RuCB displayed the most attractive photophysical properties in solution (λem 635 nm, τT 2.53 μs, and φp 20.4 %).
A multitude of microparticles and nanoparticles is developed to improve the delivery of different small drugs and large biomolecules, which are subject to several hindering biological barriers that limit their optimal biodistribution and therapeutic effects. Here, a soft, reliable, and scalable method based on compressed CO2 is reported for obtaining nanoconjugates of recombinant human epidermal growth factor and nanovesicles called quatsomes, where the latter consists of cholesterol and cetyltrimethylammonium bromide.These nanoconjugates exhibit appropriate values of the major critical quality attributes of colloidal nanomedicines, such as controlled and narrow nanoscopic particle size distribution (which play important roles in determining their stability), drug loading, drug release, drug protection, targeting ability, and bioactivity.
The use of surgical meshes to reinforce damaged internal soft tissues has been instrumental for successful hernia surgery; a highly prevalent condition affecting yearly more than 20 million patients worldwide. Intraperitoneal adhesions between meshes and viscera are one of the most threatening complications, often implying reoperation or side effects such as chronic pain and bowel perforation.
Limbal stem cells (LSCs) are already used in cell‐based treatments for ocular surface disorders. Clinical translation of LSCs‐based therapies critically depends on the successful delivery, survival, and retention of these therapeutic cells to the desired region. Such a major bottleneck could be overcome by using an appropriate carrier to provide anchoring sites and structural support to LSC culture and transplantation.