Silica Nanoparticles with Virus-Mimetic Spikes Enable Efficient siRNA Delivery In Vitro and In Vivo
Jianye Fu,
Wenwei Han,
Xue Zhang,
Yutong Sun,
Rajendra Bhadane,
Bo Wei,
Li Li,
Liangmin Yu,
Jinbo Yang,
Jessica M. Rosenholm,
Outi M. H. Salo-Ahen,
Taojian Fan,
Bin Zhang,
Wageh Swelm,
Ahmed A. Al-Ghamdi,
Lin Xia,
Han Zhang,
Meng Qiu,
Hongbo Zhang,
Xin Wang
Affiliations
Jianye Fu
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Wenwei Han
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Xue Zhang
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Yutong Sun
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Rajendra Bhadane
Pharmaceutical Sciences Laboratory, Åbo Akademi University, 20520 Turku, Finland.
Bo Wei
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Li Li
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Liangmin Yu
Key Laboratory of Marine Chemistry Theory and Technology (Ocean University of China), Ministry of Education, Qingdao 266100, China.
Jinbo Yang
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Jessica M. Rosenholm
Pharmaceutical Sciences Laboratory, Åbo Akademi University, 20520 Turku, Finland.
Outi M. H. Salo-Ahen
Pharmaceutical Sciences Laboratory, Åbo Akademi University, 20520 Turku, Finland.
Taojian Fan
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.
Bin Zhang
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.
Wageh Swelm
Department of Physics, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Ahmed A. Al-Ghamdi
Department of Physics, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Lin Xia
Hangzhou No. 14 High School, Hangzhou 310000, China.
Han Zhang
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.
Meng Qiu
Key Laboratory of Marine Chemistry Theory and Technology (Ocean University of China), Ministry of Education, Qingdao 266100, China.
Hongbo Zhang
Pharmaceutical Sciences Laboratory, Åbo Akademi University, 20520 Turku, Finland.
Xin Wang
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
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.
