Astrocyte-targeted siRNA delivery by adenosine-functionalized LNP in mouse TBI model.
- Resource Type
- Academic Journal
- Authors
- Xiao H; Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.; Amarsaikhan O; Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.; Zhao Y; Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.; Yu X; Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.; Hu X; Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.; Han S; Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.; Chaolumen; Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.; Baigude H; Inner Mongolia Key Laboratory of Mongolian Medicinal Chemistry, School of Chemistry & Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia 010020, P.R. China.
- Source
- Publisher: Cell Press Country of Publication: United States NLM ID: 101581621 Publication Model: eCollection Cited Medium: Print ISSN: 2162-2531 (Print) Linking ISSN: 21622531 NLM ISO Abbreviation: Mol Ther Nucleic Acids Subsets: PubMed not MEDLINE
- Subject
- Language
- English
- ISSN
- 2162-2531
Traumatic brain injury (TBI) induces pro-inflammatory polarization of astrocytes and causes secondary disruption of the blood-brain barrier (BBB) and brain damage. Herein, we report a successful astrocyte-targeted delivery of small interfering RNA (siRNA) by ligand functionalized lipid nanoparticles (LNPs) formulated from adenosine-conjugated lipids and a novel ionizable lipid (denoted by Ad4 LNPs). Systemic administration of Ad4 LNPs carrying siRNA against TLR4 to the mice TBI model resulted in the specific internalization of the LNPs by astrocytes in the vicinity of damaged brain tissue. A substantial knockdown of TLR4 at both mRNA and protein levels in the brain was observed, which led to a significant decrease of key pro-inflammatory cytokines and an increase of key anti-inflammatory cytokines in serum. Dye leakage measurement suggested that the Ad4-LNP-mediated knockdown of TLR4 attenuated the TBI-induced BBB disruption. Together, our data suggest that Ad4 LNP is a promising vehicle for astrocyte-specific delivery of nucleic acid therapeutics.
Competing Interests: The authors declare no competing interests.
(© 2023 The Author(s).)