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The role of disulfide-bridge on the activities of H-shape gemini-like cationic lipid based siRNA delivery.
Ma, Xiao-Fei; Sun, Jing; Qiu, Chong; Wu, Yi-Fan; Zheng, Yi; Yu, Min-Zhi; Pei, Xi-Wei; Wei, Lin; Niu, Yu-Jie; Pang, Wen-Hao; Yang, Zhen-Jun; Wang, Jian-Cheng; Zhang, Qiang.
Afiliación
  • Ma XF; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China.
  • Sun J; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China.
  • Qiu C; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China.
  • Wu YF; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China.
  • Zheng Y; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China.
  • Yu MZ; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China.
  • Pei XW; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China.
  • Wei L; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China.
  • Niu YJ; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China.
  • Pang WH; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China.
  • Yang ZJ; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China. Electronic address: yangzj@bjmu.edu.cn.
  • Wang JC; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China. Electronic address: wang-jc@bjmu.edu.cn.
  • Zhang Q; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 38 Xueyuan Road, 100191, China.
J Control Release ; 235: 99-111, 2016 08 10.
Article en En | MEDLINE | ID: mdl-27242198
In our previous study, a H-shape gemini-like cationic lipid (ssGLCL, formerly named as CLD), composed of two hydrophilic lysine heads and two hydrophobic oleyl alcohol tails with a bridge of the redox-active disulfide-bond, had been synthesized and used as a nanocarrier for delivering small interfering RNAs (siRNAs) into cells. In order to further elucidate the role of disulfide (-S-S-) bridge on the activity of ssGLCL based siRNA delivery, a comparable ccGLCL bridged with a non-reducible carbon-carbon bond was synthesized and used as control in this study. Both two H-shape GLCL molecules could individually self-assemble into cationic nanoparticles in water phase and complex with negatively-charged siRNA into nanoplexes with particle size of ~200nm and zeta potential of ~ +30mV, and exhibit effective siRNA delivery both in vitro and in vivo. Investigation of internalization pathway displayed that both ssGLCL/siRNA and ccGLCL/siRNA nanoplexes were predominantly internalized into MCF-7 cells by the clathrin-mediated endocytosis pattern. Although a lower cellular uptake of siRNA was found in the human breast cancer MCF-7 cells, the ssGLCL/siRNA nanoplexes could exhibit similar or even stronger down-regulation effects on the targeted EGFR mRNA and protein in MCF-7 cells when compared to the ccGLCL/siRNA nanoplexes. Furthermore, mechanistic study showed that the enhanced down-regulation effects of ssGLCL/siRNA nanoplexes on targeted mRNA and protein were probably attributed to the increased release of siRNA from lysosomes to cytoplasm following the cleavage of redox-active disulfide-bridge in ssGLCL. Therefore, we believed that the redox-active H-shape ssGLCL could be a potential nanocarrier towards improving siRNA delivery.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Técnicas de Transferencia de Gen / ARN Interferente Pequeño / Disulfuros / Nanopartículas / Lípidos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Técnicas de Transferencia de Gen / ARN Interferente Pequeño / Disulfuros / Nanopartículas / Lípidos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos