Title : Lipid nanoparticle-assisted miR29a delivery based on core-shell nanofibers improves tendon healing by cross-regulation of the immune response and matrix remodeling
Abstract:
It’s well known that transfecting siRNA into recipient cells is challenging due to the high hydrophilicity, high molecular weight and anionic charge of siRNA. What’s worse, siRNA is quickly degraded and inactivated in vivo. Therefore, it is of urgent importance to develop a drug delivery system (DDS) that can effectively deliver genes while stabilizing siRNA. Nanoparticles have been widely used for drug delivery owing to their high surface area to volume ratio, high stability, and size modifiability. Among them, lipid nano particles have been approved for siRNA delivery by the FDA for their low toxicity, no immunogenicity and low risk of mutagenicity. Despite the advantages of low toxicity and genomic safety, liposomes still face the problem of poor transfection efficiency.
In recent study, we employed microfluidic technology to fabricate siRNA-LNPs, which exhibited efficient transfection capabilities and great endosomal escape properties. Specially, we utilized DLin- MC3-DMA, which has been reported to be an excellent cationic lipid. The use of cationic liposomes is one of the most promising schemes for optimization. Positively charged liposomes have a higher encapsulation rate. They are more easily taken up by negatively charged cell membranes and are capable of endosomal escape.
Then, we developed a microfluidic platform for LNPs synthesis, where lipid components (alcohol phase) and nucleic acid oligomers (aqueous phase) can aggregate in microchannels and self- assemble into siRNA-LNPs complexes. Microfluidic prepared siRNA-LNPs have many advantages over directly mixed lipid complexes (lipoplexes). Firstly, siRNAs are thought to be localized on the surface of lipoplexes, which makes it easier to dissociate into the medium. In contrast, siRNAs can bind inside the microfluidic prepared LNPs, thus offering better protection. Secondly, siRNA-LNPs can be incorporated into cells more efficiently in a co-assembled state, and the amount of siRNA internalized into the cells is higher. Third, siRNA-LNPs seemed to cause fewer inflammatory responses than lipoplexes.
In conclusion, we prepared optimized lipid nanoparticles by microfluidics for the delivery of siRNA, which exhibited efficient transfection capabilities.
