Trehalose-releasing nanogels: A step toward a trehalose delivery vehicle for autophagy stimulation

A Simple Synthesis of Reduction-Responsive Acrylamide-Type Nanogels for miRNA Delivery

“…Stimulus-responsive nanogels have been reported to be effective drug/gene delivery systems for the diagnosis and treatment of various human diseases [ 10 , 11 ]. In our previous study, we developed acrylamide-based trehalose-containing nanogels for autophagy modulation [ 24 ] and anionic biodegradable nanogels with high doxorubicin (DOX) loading capacity to prevent DOX from aggregating in biological media and enhance the release of DOX via pH/reduction stimuli [ 25 ]. In the design of miRNA-loaded nanogels, we used the same synthetic approach, the only differences being the monomer composition and initiator concentration.…”

“…Degradable nanogels were synthesized via free-radical polymerization (FRP) in an inverse w/o mini-emulsion according to our previous method [ 24 , 25 ]. A w/o mini-emulsion (10:1, v / v ) was composed of 10.0 mL of cyclohexane containing Span-80 (600 mg) and 1.0 mL of PB solution (pH 7.0) containing monomers.…”

Trehalose-Bearing Carriers to Target Impaired Autophagy and Protein Aggregation Diseases

“…36 Another strategy to target autophagy induction has been developed in our lab and concerns trehalose-rich nanogels with covalently attached but releasable trehalose. 35 The nanogels are designed on the basis of the previous studies on bulk hydrogels, which have shown that specific composition of polymeric network could ensure prolonged release of trehalose under physiologically relevant conditions. 39 As demonstrated, copolymerizing 6-O-acryloyl-trehalose with acrylamide-type monomers allows the fabrication of materials that can sustainably release trehalose at pH 7.4 due to the interaction of the amide protons with the ester bond in adjacent acrylate units, which strongly accelerates ester hydrolysis (Figure 4A).…”

“…In vivo studies on transgenic zebrafish and Drosophila larvae show that cationic trehalose-releasing nanogels can significantly induce autophagy, as indicated by the increased levels of LC3 and autophagy-related protein Atg8 and downregulation of p62 levels, thereby proving their promising potential as trehalose delivery vehicles for autophagy stimulation. 35 Recent nanosystems containing trehalose-conjugates have been fabricated by rapid mixing of amphiphilic trehalose− nucleolipid conjugates into solid lipid nanoparticles or by encapsulation of trehalose−nucleolipid conjugates into poly-(lactic-co-glycolic acid) nanoparticles through nanoprecipitation. 34 In both cases, thymidine-based lipids are coupled to trehalose through an ester moiety, which allows its enzymatic release in neuronal cells.…”

“…Another strategy to target autophagy induction has been developed in our lab and concerns trehalose-rich nanogels with covalently attached but releasable trehalose . The nanogels are designed on the basis of the previous studies on bulk hydrogels, which have shown that specific composition of polymeric network could ensure prolonged release of trehalose under physiologically relevant conditions .…”