It aims to analyze the work of American International Association for Economic and Social Development (AIA), a philanthropic agency founded by Nelson Rockefeller, between 1946 and 1961 in Brazil. Aiming to promote b...It aims to analyze the work of American International Association for Economic and Social Development (AIA), a philanthropic agency founded by Nelson Rockefeller, between 1946 and 1961 in Brazil. Aiming to promote better standards of living to the Latin American rural population, AIA is merged in a historical context of increasing US economic and politic influence over Latin America and Brazil, diffusing and adapting US technical assistance programs to local contexts. However, this research developed the idea of an intense process of political negotiation, including resistance from Brazilian political staff. Also, there were many difficulties in adapting these programs to the local context, leading to constant reorganization of the AIA's work in Brazil.展开更多
Incorporating functional ligands and biodegradable bonds into biocompatible low-molecular-weight(LMW)polymers,such as 1.8 kDa poly(ethylenimine)(PEI1.8 k),is a common strategy to improve the properties of LMW polymers...Incorporating functional ligands and biodegradable bonds into biocompatible low-molecular-weight(LMW)polymers,such as 1.8 kDa poly(ethylenimine)(PEI1.8 k),is a common strategy to improve the properties of LMW polymers including biosafety and delivery efficacy.This study demonstrates the hypothesis that introducing different functional ligands and linked reductive disulfides in PEI 1.8k will achieve superior siRNA transfection efficiency.By incorporating PEI-X(X represents cholesterol(Ch),heptafluorobutyric anhydride(HFBA,F)and 4-carboxyphenylboronic acid(PBA))functional ligands into PEI 1.8k and subsequently crosslinking with each other via disulfide bond links,reductive-responsive PEI-X-SS-X-PEI copolymers were constructed to enhance the cellular transfection via the synergistic effect of the high affinity of Ch,F and PBA to cell membranes and the disulfide reduction triggered intracellular disassembly of micelles and subsequent siRNA release.Extraordinarily,ternary Ch-SS-F-SS-PBA micelles exhibited the strongest siRNA transfection efficiencies in in vitro cell experiments and in vivo animal experiments due to the coordination of enhanced serum stability,promoted cell uptake and endosomal escape,and cell targeting ability.This strategy of constructed multifunctional polymer here we called"building-block crosslinking"showed a simple and smart way to synthesize new materials.Also this strategy of constructing ligands-directed reduction-sensitive micelles improves the transfection efficiency of LMW PEI and provides a valuable insight to develop novel gene delivery systems.展开更多
文摘It aims to analyze the work of American International Association for Economic and Social Development (AIA), a philanthropic agency founded by Nelson Rockefeller, between 1946 and 1961 in Brazil. Aiming to promote better standards of living to the Latin American rural population, AIA is merged in a historical context of increasing US economic and politic influence over Latin America and Brazil, diffusing and adapting US technical assistance programs to local contexts. However, this research developed the idea of an intense process of political negotiation, including resistance from Brazilian political staff. Also, there were many difficulties in adapting these programs to the local context, leading to constant reorganization of the AIA's work in Brazil.
基金supported by the National Natural Science Foundation of China(81903556)the Natural Science Fund for Colleges and Universities in Jiangsu Province(19KJB350004)supported by the National Health and Medical Research Council(NHMRC)Early Career Fellowship(1112258)of Australia。
文摘Incorporating functional ligands and biodegradable bonds into biocompatible low-molecular-weight(LMW)polymers,such as 1.8 kDa poly(ethylenimine)(PEI1.8 k),is a common strategy to improve the properties of LMW polymers including biosafety and delivery efficacy.This study demonstrates the hypothesis that introducing different functional ligands and linked reductive disulfides in PEI 1.8k will achieve superior siRNA transfection efficiency.By incorporating PEI-X(X represents cholesterol(Ch),heptafluorobutyric anhydride(HFBA,F)and 4-carboxyphenylboronic acid(PBA))functional ligands into PEI 1.8k and subsequently crosslinking with each other via disulfide bond links,reductive-responsive PEI-X-SS-X-PEI copolymers were constructed to enhance the cellular transfection via the synergistic effect of the high affinity of Ch,F and PBA to cell membranes and the disulfide reduction triggered intracellular disassembly of micelles and subsequent siRNA release.Extraordinarily,ternary Ch-SS-F-SS-PBA micelles exhibited the strongest siRNA transfection efficiencies in in vitro cell experiments and in vivo animal experiments due to the coordination of enhanced serum stability,promoted cell uptake and endosomal escape,and cell targeting ability.This strategy of constructed multifunctional polymer here we called"building-block crosslinking"showed a simple and smart way to synthesize new materials.Also this strategy of constructing ligands-directed reduction-sensitive micelles improves the transfection efficiency of LMW PEI and provides a valuable insight to develop novel gene delivery systems.