Gold nanoparticles decorated with monosaccharides and sulfated ligands as potential modulators of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS).

N-Acetylgalactosamine-6-sulfatase (GALNS) is an enzyme whose deficiency is related to the lysosomal storage disease Morquio A. For the development of effective therapeutic approaches against this disease, the design of suitable enzyme enhancers (i.e. pharmacological chaperones) is fundamental. The natural substrates of GALNS are the glycosaminoglycans keratan sulfate and chondroitin 6-sulfate, which mainly display repeating units of sulfated carbohydrates. With a biomimetic approach, gold nanoparticles (AuNPs) decorated with simple monosaccharides, sulfated ligands (homoligand AuNPs), or both monosaccharides and sulfated ligands (mixed-ligand AuNPs) were designed here as multivalent inhibitors of GALNS. Among the homoligand AuNPs, the most effective inhibitors of GALNS activity are the ß-D-galactoside-coated AuNPs. In the case of mixed-ligand AuNPs, ß-D-galactosides/sulfated ligands do not show better inhibition than the ß-D-galactoside-coated AuNPs. However, a synergistic effect is observed for α-D-mannosides in a mixed-ligand coating with sulfated ligands that reduced IC50 by one order of magnitude with respect to the homoligand α-D-mannoside-coated AuNPs. SAXS experiments corroborated the association of GALNS with ß-D-galactoside AuNPs. These AuNPs are able to restore the enzyme activity by almost 2-fold after thermal denaturation, indicating a potential chaperoning activity towards GALNS. This information could be exploited for future development of nanomedicines for Morquio A. The recent implications of GALNS in cancer and neuropathic pain make these kinds of multivalent bionanomaterials of great interest towards multiple therapies.

Subcritical Hydrothermal Liquefaction as a Pretreatment for Enzymatic Degradation of Polyurethane.

Enzymatic digestion is a promising alternative in the upconversion of plastic waste compared to traditional chemical recycling methods, because it warrants the use of milder conditions. However, enzymes are hardly able to penetrate the bulk of the plastic material; thus, a pretreatment is necessary to promote the reaction. In this study we investigate hydrothermal liquefaction as a thermal pretreatment of a commercial polyurethane before performing an enzymatic digestion. The feedstock is a rigid polyurethane foam. The structure and chemical composition of the feedstock were analyzed through FTIR analysis and solid-state 13C NMR. The polyurethane was then subjected to hydrothermal liquefaction using either ultrapure water or KOH as a basic catalyst. Enzymatic digestion was then performed on the organic fraction obtained from both experiments using a lipase extracted from Candida rugosa. The LC-MS analysis of the digests shows an increase in some signal intensities due to the degradation of oligomeric fragments. This new way of recycling allows the recovery of important chemicals such as quinolines and 4,4'-methylenedianiline. With this study we demonstrate that hydrothermal liquefaction coupled with enzymatic digestion is a suitable alternative for handling polyurethane waste.