TY - JOUR
T1 - Silica Nanoparticles with Virus-Mimetic Spikes Enable Efficient siRNA Delivery In Vitro and In Vivo
AU - Fu, Jianye
AU - Han, Wenwei
AU - Zhang, Xue
AU - Sun, Yutong
AU - Bhadane, Rajendra
AU - Wei, Bo
AU - Li, Li
AU - Yu, Liangmin
AU - Yang, Jinbo
AU - Rosenholm, Jessica M.
AU - Salo-Ahen, Outi M.H.
AU - Fan, Taojian
AU - Zhang, Bin
AU - Swelm, Wageh
AU - Al-Ghamdi, Ahmed A.
AU - Xia, Lin
AU - Zhang, Han
AU - Qiu, Meng
AU - Zhang, Hongbo
AU - Wang, Xin
N1 - Publisher Copyright:
Copyright © 2022 Jianye Fu et al. Exclusive Licensee Science and Technology Review Publishing House. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License (CC BY 4.0)
PY - 2022
Y1 - 2022
N2 - 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 (NH2-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 NH2-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.
AB - 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 (NH2-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 NH2-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.
UR - https://www.scopus.com/pages/publications/85147731634
U2 - 10.34133/RESEARCH.0014
DO - 10.34133/RESEARCH.0014
M3 - 文章
AN - SCOPUS:85147731634
SN - 2096-5168
VL - 2022
JO - Research
JF - Research
M1 - 0014
ER -