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 suffe...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.展开更多
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)+8 种基金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.
文摘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.
