Silica Nanoparticles with Virus-Mimetic Spikes Enable Efficient siRNA Delivery In Vitro and In Vivo  

作　　者：Jianye Fu Wenwei Han Xue Zhang Yutong Sun Rajendra Bhadane Bo Wei Li Li Liangmin Yu Jinbo Yang Jessica MRosenholm Outi MHSalo-Ahen Taojian Fan Bin Zhang Wageh Swelm Ahmed AAl-Ghamdi Lin Xia Han Zhang Meng Qiu Hongbo Zhang Xin Wang 

机构地区：[1]Key Laboratory of Marine Drugs,Chinese Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China [2]Collaborative Innovation Center for Optoelectronic Science&Technology,International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education,Institute of Microscale Optoelectronics,College of Physics and Optoelectronic Engineering,Shenzhen University,Shenzhen 518060,China [3]Key Laboratory of Marine Chemistry Theory and Technology(Ocean University of China),Ministry of Education,Qingdao 266100,China [4]College of Chemistry and Chemical Engineering,China University of Petroleum,Qingdao 266555,China. [5]Pharmaceutical Sciences Laboratory,Åbo Akademi University,20520 Turku,Finland [6]Structural Bioinformatics Laboratory,Biochemistry,Åbo Akademi University,20520 Turku,Finland. [7]Center for Innovation Marine Drug Screening&Evaluation,Pilot National Laboratory for Marine Science and Technology(Qingdao),Qingdao 266237,China [8]Marine Biomedical Research Institute of Qingdao,Qingdao 266100,China [9]Department of Physics,Faculty of Science,King Abdulaziz University,Jeddah 21589,Saudi Arabia [10]Hangzhou No.14 High School,Hangzhou 310000,China [11]Turku Bioscience Centre,University of Turku andÅbo Akademi University,20520 Turku,Finland

出　　处：《Research》2023年第3期281-294,共14页研究（英文）

基　　金：the National Natu ral Science Foundation of China(U22A20582,X.W.,22005197,J.F.,61435010 and 61575089,Han Z.,U1803128,M.Q.,81991525,X.W.,81871472,Han Z.);the Natural Science Founda-tion of Shandong Province(ZR202110150015,ZR2021LSW013,ZR202110290057);the China Postdoctoral Science Foun-dation(Grant No.2021M692197,J.F.);State Key Research Development Program of China(2019YFB2203503,Han Z.);the Science and Technology Innovation Commission of Shenzhen(KQTD2015032416270385,JCYJ20150625103619275,Han Z.,JCYJ20180305124854790,M.Q.);the Natural Science Foun-dation of Guangdong Province(2018A030310500);the Taishan Scholar Project(tsqn201909054,tsqn201909170);the Fundamental Research Funds for the Central Universities to X.W.and M.Q.,and Tor,Joe and Pentti Borg Memorial Fund(R.B.).This project was funded by the Deanship of Scientific Research(DSR)at King Abdulaziz University,Jeddah,under grant no.(KEP-MSc-70-130-42).;The Research Fellow(Grant No.328933);Solutions for Health Profile(336355);InFLAMES Flagship(337531)projects from Academy of Finland,as well as the Finland-China Food and Health(FCFH)International Pilot Project funded by the Finnish Ministry of Education and Culture are acknowledged.

摘　　要：Oligonucleotide-based therapy has experienced remarkable development in the past 2 decades,but its broad applications are severely hampered by delivery vectors.Widely used viral vectors and lipid nanovectors are suffering from immune clearance after repeating usage or requiring refrigerated transportation and storage,respectively.In this work,amino-modified virus-mimetic spike silica nanoparticles(NH_(2)-SSNs)were fabricated using a 1-pot surfactant-free approach with controlled spike lengths,which were demonstrated with excellent delivery performance and biosafety in nearly all cell types and mice.It indicated that NH2-SSNs entered cells by spike-dependent cell membrane docking and dynamin-dependent endocytosis.The positively charged spikes with proper length on the surface can facilitate the efficient encapsulation of RNAs,protect the loaded RNAs from degradation,and trigger an early endosome escape during intracellular trafficking,similarly to the cellular internalization mechanism of virions.Regarding the fantastic properties of NH_(2)-SSNs in nucleic acid delivery,it revealed that nanoparticles with solid spikes on the surface would be excellent vehicles for gene therapy,presenting self-evident advantages in storage,transportation,modification,and quality control in large-scale production compared to lipid nanovectors.

关 键 词：SURFACTANT loaded TRANSPORTATION 

分 类 号：R73[医药卫生—肿瘤]