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

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.

Hierarchical dual-porous hydroxyapatite doped dendritic mesoporous silica nanoparticles based scaffolds promote osteogenesis in vitro and in vivo

Biomaterial based scaffolds for treating large bone defects require excellent biocompatibility and osteoconductivity.Here we report on the fabrication of hydroxyapatite-dendritic mesoporous silica nanoparticles(HA-DMSN)based scaffolds with hierarchical micro-pores(5µm)and nano-pores(6.4 nm),and their application for bone regeneration.The in vitro studies demonstrated good biocompatibility of dissolution extracts,as well as enhanced osteogenic potential indicated by dose-dependent upregulation of bone marker gene expression(osteocalcin gene(OCN),osteopontin gene(OPN),collagen type I alpha 1 gene(CoL1A1),runt-related transcription factor 2 gene(RUNX2),and integrin-binding sialoprotein gene(IBSP)),alkaline phosphatise(ALP)activity,and alizarin red staining.The in vivo studies showed that HA-DMSN scaffolds significantly increased bone formation in a rat cranial bone defect model after 4 weeks healing.Our study provides a simple method to fabricate promising inorganic scaffolds with hierarchical pores for bone tissue engineering.