title: Single-component self-assembled RNAi nanoparticles functionalized with tumor-targeting iNGR delivering abundant siRNA for efficient glioma therapy.
abstract: Existing limitations of common RNA interference (RNAi) oncotherapy severely compromised their therapeutic effects. In this study, a novel glioma-targeting RNAi system was developed. Single-component RNAi nanospheres were tactfully self-assembled in vitro, combining the carrier and cargo as a whole. An artificially synthesized polycation (pOEI) with redox-sensitive disulfides in structure condensed the RNAi nanospheres into more compacted nanoparticles. Then a novelly designed tumor-homing and penetrating cyclopeptide iNGR was further modified on the surface. iNGR modified RNAi nanoparticles demonstrated significantly enhanced accumulation in glioma site, remaining stable in circulation until the release of naked RNAi nanospheres were triggered off by the paranormal concentration of glutathione within glioma cells. Naked RNAi nanospheres were digested into abudant siRNA afterwards. Remarkable luciferase gene down-regulations have confirmed their outstanding RNAi effects. With specific design of sequences, the iNGR modified RNAi nanoparticles were supposed to be of great potential in safe and efficient glioma therapy in future.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Sai
authors.initials: S
authors.lastname: An
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Xutao
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Jiashu
authors.initials: J
authors.lastname: Shi
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Xi
authors.initials: X
authors.lastname: He
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Haojun
authors.initials: H
authors.lastname: Ma
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China; State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China. Electronic address: jiangchen@shmu.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy*; D005910:Glioma / Q000628:therapy*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D009842:Oligopeptides / Q000737:chemistry*; D010084:Oxidation-Reduction; D034622:RNA Interference
chemical_list: D009842:Oligopeptides; C579134:cysteinyl-arginyl-asparagyl-glycyl-arginyl-glycyl-prolyl-aspartyl-cysteine
keywords: Glioma therapy; Glutathione triggered; RNAi; Self-assembled nanoparticle; Tumor-homing and penetrating; iNGR