Enhanced intrapulmonary delivery of anticancer siRNA using cationic liposome for lung cancer therapy

pulmonary delivery;siRNA;cationic nanoliposomes;lung cancer

약학대학 약학과 ;

University:서울대학교 대학원

关键词: pulmonary delivery;    siRNA;    cationic nanoliposomes;    lung cancer;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/133439/1/000000004734.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

Here we report a cationic nanolipoplex for pulmonary cellular delivery system of siRNA. Six nanoliposomes differing in cationic lipids were formulated and screened at in vitro and in vivo for cellular delivery functions in lung tissues. Although the six nanoliposomes showed similar siRNA delivery efficiency in vitro, they exhibited significant differences in vivo pulmonary cellular delivery functions. Among the various nanoliposomes, cationic dioleoyl-sn-glycero-3-ethylphosphocholine- and cholesterol-based nanoliposomes (ECL) showed the highest pulmonary cellular delivery in vivo and the lowest cytotoxicity in vitro. The fluorescent siRNA delivery efficiency of ECL nanoliposomes was 26.2-fold higher than that of naked siRNA in vivo. The treatment of Mcl1-specific siMcl1 using ECL nanolipoplexes provided the reduction of target gene in B16F10 cell lines, whereas luciferase-specific siGL2 in ECL nanolipoplexes did not provide the reduction of the target gene. In B16F10 metastasized lung cancer model in mice, the intratracheal administration of siMcl1 in ECL nanolipoplexes revealed the lower formation of tumor nodules in the lung. Moreover, the intratracheal delivery of siMcl1 in ECL nanolipoplexes showed the significant silencing of Mcl1 in mRNA and protein levels at the lung tissue. These results indicate the utility of ECL nanoliposomes for pulmonary delivery of therapeutic siRNA for the treatment of lung cancers and potentially for other respiratory diseases.