Cationic lipids have been applied to siRNA delivery for tumor therapeutics. However, the excess positive charges of these nanoplexes may lead to high cytotoxicity and nonnegligible immunogenicity both in vitro and in ...Cationic lipids have been applied to siRNA delivery for tumor therapeutics. However, the excess positive charges of these nanoplexes may lead to high cytotoxicity and nonnegligible immunogenicity both in vitro and in vivo, which limited the applications of gene drugs. We constructed multi-component lipoplex to delivery 3',3"-bis-peptide-siRNA conjugate (pp-siRNA) by the treatment of melanoma. Based on the previous studies that the gemini lipid (CLD) encapsulated pp-siRNA, a novel neutral cytosin-l-yl- lipid (DNCA) was considered to replace a certain ration of CLD by hydrogen bonds and ~t-n stacking for reducing the cytotoxicity. It similarly retained in both the loading efficiency and targeted mRNA inhibition when DNCA was accounted for 40% in the lipoplex, with lower toxicity. Moreover, CLD/DNCA/pp-siRNA nanoplex could be uptake in A375 cells and internalized mainly by macropinocytosis and caveolin-mediated endocytosis. Besides, 90% CLD/DNCA/pp-siRNA nanoplexes presented the highest efficient knockdown for the mutant B-RAF mRNA (-80%). All the results demonstrated that the mixed cationic and neutral lipids could efficiently realize the delivery of pp-siRNA and had potential application for cancer therapy.展开更多
The white upconversion luminescence (UCL) of upconversion nanoparticles (UCNPs) is mainly made up of the color red, green and blue. Interestingly, the white-light-emitting UCNPs can be obtained via a complex metho...The white upconversion luminescence (UCL) of upconversion nanoparticles (UCNPs) is mainly made up of the color red, green and blue. Interestingly, the white-light-emitting UCNPs can be obtained via a complex method of tridoping lanthanide ions such as Yb^3+, Er^3+, and Tm^3+. We herein report that an excellent white UCL can be obtained from Yb/Tm double-doped ZnO. In this system, the blue and red UCL-emissions around 475 and 652 nm originate from ^1G4→^3H6 and ^1G4→^3F4 transition of Tm^3+, respectively, and the green one can be attributed to the defect states (oxygen va- cancies) luminescence (DSL) of the ZnO host. Meanwhile, the fine nanostructure of ZnO:Yb/Tm is prepared by adjusting the concentration of OH-. Particularly, the one dimentional pencil-shaped nanorods with high aspect ratio achieve a strong green DSL emission due to the high concentration of oxygen vacancy. The oxygen vacancy defects play an irreplaceable role in affecting the intensities of blue and red UCL by acting as the intermediate state in the energy transfer process. More importantly, we demonstrate that the DSL and UCL can be combined into systems, paving a new road for obtaining the white UCL emission.展开更多
基金The National Natural Science Foundation of China(Grant No.21778006 and 20932001)the Ministry of Science and Technology of China(Grant No.2012AA022501)
文摘Cationic lipids have been applied to siRNA delivery for tumor therapeutics. However, the excess positive charges of these nanoplexes may lead to high cytotoxicity and nonnegligible immunogenicity both in vitro and in vivo, which limited the applications of gene drugs. We constructed multi-component lipoplex to delivery 3',3"-bis-peptide-siRNA conjugate (pp-siRNA) by the treatment of melanoma. Based on the previous studies that the gemini lipid (CLD) encapsulated pp-siRNA, a novel neutral cytosin-l-yl- lipid (DNCA) was considered to replace a certain ration of CLD by hydrogen bonds and ~t-n stacking for reducing the cytotoxicity. It similarly retained in both the loading efficiency and targeted mRNA inhibition when DNCA was accounted for 40% in the lipoplex, with lower toxicity. Moreover, CLD/DNCA/pp-siRNA nanoplex could be uptake in A375 cells and internalized mainly by macropinocytosis and caveolin-mediated endocytosis. Besides, 90% CLD/DNCA/pp-siRNA nanoplexes presented the highest efficient knockdown for the mutant B-RAF mRNA (-80%). All the results demonstrated that the mixed cationic and neutral lipids could efficiently realize the delivery of pp-siRNA and had potential application for cancer therapy.
基金supported by the National Natural Science Foundation of China (11374080)
文摘The white upconversion luminescence (UCL) of upconversion nanoparticles (UCNPs) is mainly made up of the color red, green and blue. Interestingly, the white-light-emitting UCNPs can be obtained via a complex method of tridoping lanthanide ions such as Yb^3+, Er^3+, and Tm^3+. We herein report that an excellent white UCL can be obtained from Yb/Tm double-doped ZnO. In this system, the blue and red UCL-emissions around 475 and 652 nm originate from ^1G4→^3H6 and ^1G4→^3F4 transition of Tm^3+, respectively, and the green one can be attributed to the defect states (oxygen va- cancies) luminescence (DSL) of the ZnO host. Meanwhile, the fine nanostructure of ZnO:Yb/Tm is prepared by adjusting the concentration of OH-. Particularly, the one dimentional pencil-shaped nanorods with high aspect ratio achieve a strong green DSL emission due to the high concentration of oxygen vacancy. The oxygen vacancy defects play an irreplaceable role in affecting the intensities of blue and red UCL by acting as the intermediate state in the energy transfer process. More importantly, we demonstrate that the DSL and UCL can be combined into systems, paving a new road for obtaining the white UCL emission.