A1 Refereed original research article in a scientific journal

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




AuthorsFu Jianye, Han Wenwei, Zhang Xue, Sun Yutong, Bhadane Rajendra, Wei Bo, Li Li, Yu Liangmin, Yang Jinbo, Rosenholm Jessica M, Salo-Ahen Outi MH, Fan Taojian, Zhang Bin, Swelm Wageh, Al-Ghamdi Ahmed A, Xia Lin, Zhang Han, Qiu Meng, Zhang Hongbo, Wang Xin

PublisherAMER ASSOC ADVANCEMENT SCIENCE

Publication year2022

JournalResearch

Journal name in sourceRESEARCH

Journal acronymRESEARCH-CHINA

Article number 0014

Volume2022

Number of pages14

ISSN2096-5168

eISSN2639-5274

DOIhttps://doi.org/10.34133/research.0014

Web address https://spj.science.org/doi/10.34133/research.0014

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/178965598


Abstract

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.


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Last updated on 2024-26-11 at 13:14