Intracellularly biotriggered decomposition of gene vectors is generally thought to benefit transfection. However, the bioresponsiveness is far from satisfactory, and the exact role of biodecomposition in the transfection process remains unclear to date. To overcome the challenges, highly rapid bioresponse of vectors has to be achieved so as to greatly amplify the intracellular deviation compared with the noncontrolled pattern. To this end, a supramolecular polyrotaxane has been elaborately designed by integrating reversible dynamics of supramolecular assembly and chemically labile bonds, in order to effectively propel intracellular decomposition. Inside tumor cells, the redox-responsive bulk dissociation of the supramolecular vector readily took place and was further accelerated by the lysosomal-acidity-triggered terminal decomposition. Both the in vitro and in vivo experiments have demonstrated that this supramolecule could mediate considerably more rapid gene accumulation in nuclei than the nonresponsive controls including PEI25K, the gold standard of nonviral vectors. Along with the structural decomposition, the supramolecule simultaneously underwent the transition of fluorescence quenching, favoring the evaluation over the bioresponsiveness inside cells. Based on the resulting data, it is suggested that the biotriggered volume expansion of supramolecule/DNA complexes may be the major factor accounting for that dramatically accelerated transnuclear gene transport during cellular mitosis, thus affecting the transfection. This study offers an understanding of the intracellular gene transport from a new viewpoint.
Recent advances in nanomaterials have made iron oxide nanoparticles (IONPs) as an innovative approach for the delivery of genes. However, the effectiveness of IONPs-assisted gene delivery is currently suffering from their poor uniformity, which not only exhibits detrimental effect on the magnetic property, but also leads to the poor reproducibility to maintain the optimal gene delivery. To this end, the present study developed extremely uniform 15 nm-sized IONPs with a good monodispersity in water phase. These ultra-uniform IONPs exhibit notable potentials for an efficient gene delivery to human mesenchymal stem cells (hMSCs) with the assistance of magnetic force, which partly owes to their abilities to facilitate the cellular uptake, as well as to induce the rapid DNA release and the following nuclear transport. Besides, no significant detrimental effects of these IONPs are observed either on the proliferation or the multi-lineage differentiation potential of hMSCs. The current study highlights the potential advantages of designing extremely uniform magnetic nanomaterials for an efficient and safe delivery of genes to stem cells.
Li Li,Mingjie Xia,Lina Yang,Yutang He,He Liu,Mengxi Xie,Miao Yu
Polysaccharides impact intestinal fermentation and regulate interfacial properties which affect absorption and transportation. Short-chain fatty acids (SCFAs), the main metabolites of soy hull polysaccharide lysate, are readily absorbed by the body and perform various physiological functions. We analysed the interfacial properties and transport of soy hull polysaccharide-derived SCFAs in the Caco-2 cell model to clarify the transmembrane transport mechanism. The results showed that the interfacial properties of the co-culture system were influenced by both transit time and concentration of SCFAs, the uptake and transit rates of SCFAs at 1–3 h increased significantly with time ( P < 0.05). With increasing transit time and concentration, the transit rates of SCFAs on the apical side (AP) → basolateral side (BL) and BL → AP sides increased and then stabilised, the transit rate of the AP → BL side was higher than that of the BL → AP side. Proteomic analysis showed that soy hull polysaccharide-derived SCFAs resulted in the differential expression of 285 upregulated and 501 downregulated after translocation across Caco-2 cells. The differentially expressed proteins were mainly enriched in ribosomes, oxidative phosphorylation, nuclear transport, and SNARE vesicular transport. This study lays the theoretical foundation for understanding the structure-activity relationship of soy hull polysaccharides in the intestine.
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