In this study, a networked swellable dextrin nanogel （DNG） was developed to achieve stimulated responsive small interfering RNA （siRNA） release for melanoma tumor therapy, siRNA was loaded into multidimensional de...In this study, a networked swellable dextrin nanogel （DNG） was developed to achieve stimulated responsive small interfering RNA （siRNA） release for melanoma tumor therapy, siRNA was loaded into multidimensional dextrin nanogels by charge condensation with positive arginine residues modified in the dextrin backbone. Moreover, the networked nanogel was destroyed and loosened based on its bioreducible responsive property to control accelerated siRNA release in a bioreducible intracellular environment, while it remained stable under normal physiological conditions. We demonstrated that DNGs had swellable and disassembly properties under reduced buffer condition by transmission electron microscopy evaluation. The DNGs achieved an endosomal escape followed by selective release of the cargo into the cytosol by glutathione- triggered disassembly according to confocal microscopy observation. Thus, this smart nanogel achieved outstanding luciferase gene silencing efficiency and decreased Bcl2 protein expression in vitro and in vivo based on western blot analysis. Moreover, this nanogel exhibited superior anti-tumor activity for B16F10 xenograft tumors in C57BL/6 mice. These results demonstrate that the networked DNGs are effective for gene condensation and controlled intracellular release for tumor therapy. Overall, these findings suggest that this multidimensional swellable stimuli-responsive dextrin nanogel is an innovative strategy with great promise for gene and drug delivery.展开更多
We report the development of a small interfering RNA （siRNA） delivery vector based on cationic perfluorocarbon nanoemulsions. We have prepared perfluorodecalin （PFD） emulsions with a positive surface charge provid...We report the development of a small interfering RNA （siRNA） delivery vector based on cationic perfluorocarbon nanoemulsions. We have prepared perfluorodecalin （PFD） emulsions with a positive surface charge provided by a fluorinated poly（ethylenimine） （F-PEI）. The fluorinated emulsion （F-PEI@PFD） reduced cytotoxicity of F-PEI and demonstrated effective binding with siRNAs to form nanosized emulsion polyplexes. The prepared emulsion polyplexes enhanced cellular uptake and improved endosomal escape of the siRNA. In addition to increased reporter gene silencing in multiple cancer cell lines, when compared with control F-PEI and PEI polyplexes, the siR_NA emulsion polyplexes showed an excellent resistance to serum deactivation and maintained high activity, even in high-serum conditions. The F-PEI@PFD emulsion polyplexes carrying an siRNA to silence the expression of Bcl2 gene induced apoptosis and inhibited tumor growth in a melanoma mouse model in vivo and showed potential for in vivo ultrasound imaging. This study demonstrates the potential of F-PEI@PFD emulsions as a multifunctional theranostic nanoplatform for safe siRNA delivery, with integrated ultrasound imaging functionality.展开更多
文摘In this study, a networked swellable dextrin nanogel （DNG） was developed to achieve stimulated responsive small interfering RNA （siRNA） release for melanoma tumor therapy, siRNA was loaded into multidimensional dextrin nanogels by charge condensation with positive arginine residues modified in the dextrin backbone. Moreover, the networked nanogel was destroyed and loosened based on its bioreducible responsive property to control accelerated siRNA release in a bioreducible intracellular environment, while it remained stable under normal physiological conditions. We demonstrated that DNGs had swellable and disassembly properties under reduced buffer condition by transmission electron microscopy evaluation. The DNGs achieved an endosomal escape followed by selective release of the cargo into the cytosol by glutathione- triggered disassembly according to confocal microscopy observation. Thus, this smart nanogel achieved outstanding luciferase gene silencing efficiency and decreased Bcl2 protein expression in vitro and in vivo based on western blot analysis. Moreover, this nanogel exhibited superior anti-tumor activity for B16F10 xenograft tumors in C57BL/6 mice. These results demonstrate that the networked DNGs are effective for gene condensation and controlled intracellular release for tumor therapy. Overall, these findings suggest that this multidimensional swellable stimuli-responsive dextrin nanogel is an innovative strategy with great promise for gene and drug delivery.
基金This work was financially supported by the National Science and Technology Major Project （No. 2017YFA0205400）, the Changjiang Scholar program, the National Natural Science Foundation of China （Nos. 81373983 and 81573377）, China Postdoctoral Science Foundation （No. 2016M601923）, and Postgraduate Research ＆ Practice Innovation Program of Jiangsu Province （No. KYCX17_0671）.
文摘We report the development of a small interfering RNA （siRNA） delivery vector based on cationic perfluorocarbon nanoemulsions. We have prepared perfluorodecalin （PFD） emulsions with a positive surface charge provided by a fluorinated poly（ethylenimine） （F-PEI）. The fluorinated emulsion （F-PEI@PFD） reduced cytotoxicity of F-PEI and demonstrated effective binding with siRNAs to form nanosized emulsion polyplexes. The prepared emulsion polyplexes enhanced cellular uptake and improved endosomal escape of the siRNA. In addition to increased reporter gene silencing in multiple cancer cell lines, when compared with control F-PEI and PEI polyplexes, the siR_NA emulsion polyplexes showed an excellent resistance to serum deactivation and maintained high activity, even in high-serum conditions. The F-PEI@PFD emulsion polyplexes carrying an siRNA to silence the expression of Bcl2 gene induced apoptosis and inhibited tumor growth in a melanoma mouse model in vivo and showed potential for in vivo ultrasound imaging. This study demonstrates the potential of F-PEI@PFD emulsions as a multifunctional theranostic nanoplatform for safe siRNA delivery, with integrated ultrasound imaging functionality.
