title: pH-Sensitive Nanomicelles for High-Efficiency siRNA Delivery in Vitro and in Vivo: An Insight into the Design of Polycations with Robust Cytosolic Release.
abstract: The extremely low efficient cytosolic release of the internalized siRNA has emerged recently as a central issue for siRNA delivery, while there is a lack of guidelines to facilitate the cytosolic release of internalized siRNA. To address these concerns, we studied the contribution of the pH-sensitive inner core on handling the cytosolic release of siRNA delivered by a series of PG-P(DPAx-co-DMAEMAy)-PCB amphiphilic polycation nanomicelles (GDDC-Ms) with extremely low internalization (<1/4 of lipofactamine 2000 (Lipo2000)). Significantly, just by varying the mole ratio of DPA and DMAEMA to adjust the initial disassembly pH (pHdis) of the core near to 6.8, GDDC4-Ms/siRNA could get nearly 98.8% silencing efficiency at w/w = 12 with 50 nM siRNA and ∼78% silencing efficiency at w/w = 30 with a very low dose of 5 nM siRNA in HepG-2 cell lines, while Lipo2000 only got 65.7% with 50 nM siRNA. Furthermore, ∼98.4% silencing efficiency was also realized in the hard-to-transfect human acute monoblastic leukemia cell line U937 by GDDC4-Ms/siRNA (at w/w = 15, 50 nM siRNA), in the inefficient case for Lipo2000. Additionally, the high silencing efficiency (∼80%) in skin tissue in vivo was discovered. Undoubtedly, the robust potential of GDDC4-Ms in handling the cytosolic release paves a simple but efficient new way for the design of the nonviral siRNA vector.
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University , Tianjin 300072, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Yidi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University , Tianjin 300072, China.
authors.forename: Changrong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University , Tianjin 300072, China.|Department of Pharmaceutics, School of Pharmacy, Qingdao University , Qingdao 266021, China.
authors.forename: Shangcong
authors.initials: S
authors.lastname: Han
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University , Tianjin 300072, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University , Tianjin 300072, China.
authors.forename: Liandong
authors.initials: L
authors.lastname: Deng
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Deyao
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Du
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Cao
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.
authors.forename: Zicai
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University , Beijing 100871, China.
authors.forename: Yuanyu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University , Tianjin 300072, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.
authors.forename: Anjie
authors.initials: A
authors.lastname: Dong
keywords: Cytosolic release; high efficiency; low doses; low internalization; monoblastic cell; siRNA delivery