Comparison of osteogenic differentiation induced by and delivered by lipopolysaccharide-amine nanopolymersomes and underlying molecular mechanisms.

Gene therapies via small interfering (si)RNA () and bone morphogenetic protein () plasmid DNA () may be promising strategies for bone repair/regeneration, but their ideal delivery vectors, efficacy difference, and underlying mechanisms have not been explored, so these issues were probed here. This study used lipopolysaccharide-amine nanopolymersomes (LNPs), an efficient cytosolic delivery vector developed by the research team, to mediate and to transfect MC3T3-E1 cells, respectively. The cytotoxicity, cell uptake, and gene knockdown efficiency of -loaded LNPs (LNPs/) were studied, then the osteogenic-differentiation efficacy of MC3T3-E1 cells treated by LNPs/ and LNPs/, respectively, were compared by measuring the expression of osteogenesis-related genes and proteins, alkaline phosphatase (ALP) activity, and mineralization of the extracellular matrix at all osteogenic stages. Finally, the possible signaling pathways of the two treatments were explored. LNPs delivered into cells efficiently to silence 50% of expression without obvious cytotoxicity. LNPs/ and LNPs/ enhanced the osteogenic differentiation of MC3T3 E1 cells, but LNPs/ was better than LNPs/. BMP/Mothers against decapentaplegic homolog (Smad) and glycogen synthase kinase (GSK)-3β/β-catenin signaling pathways appeared to be involved in osteogenic differentiation induced by LNPs/, but GSK-3β/β-catenin was not stimulated upon LNPs/ treatment. LNPs are safe and efficient delivery vectors for DNA and RNA, which may find wide applications in gene therapy. treatment may be a more efficient strategy to enhance osteogenic differentiation than treatment. LNPs loaded with and/or may provide new opportunities for the repair and regeneration of bone.