Intranasal Delivery of Anti-Apoptotic siRNA Complexed with Fas-Signaling Blocking Peptides Attenuates Cellular Apoptosis in Brain Ischemia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Peptide
2.2. siRNA Synthesis
2.3. Gel Retardation Assay
2.4. Particle Size and Surface Charge Measurement
2.5. Atomic Force Microscopy
2.6. Cell Culture and In Vitro Hypoxia Induction
2.7. Cytotoxicity
2.8. Evaluation of siRNA Uptake Efficacy In Vitro
2.9. Evaluation of Gene-Silencing Efficacy In Vitro
2.10. Evaluation of Apoptotic Cells
2.11. Animal Studies
2.12. Localization of Intranasally Delivered FBP9R/siRNA
2.13. Evaluation of Gene-Silencing Efficacy In Vivo
2.14. Evaluation of Pathology in Brain Tissues
2.15. Immunohistochemistry
2.16. Western Blot
2.17. Statistical Analysis
3. Results
3.1. Physical Characterization of FBP9R/siRNA Nanocomplexes
3.2. FBP9R/siRNA Delivers siRNA and Induces Target Gene Silencing in Fas-Expressing Cells
3.3. FBP9R/siRNA Effectively Delivers siRNA and Induces GENE Silencing in Hypoxia-Induced Neuro-2a Cells
3.4. Intranasally Administrated FBP9R Successfully Delivers siRNA and Enables Gene Silencing in the Infarcted Hemisphere of a Rat Model of MCAO
3.5. FBP9R/siBax Attenuates the Infarcted Region and Apoptosis in the Infarcted Hemisphere in a Rat Model of Brain Ischemia
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
FBP | Fas-blocking peptide |
9R | Nona-arginine peptide |
IN | Intranasal |
MCAO | Middle cerebral artery occlusion |
siRNA | Small interference RNA |
shRNA | Short hairpin RNA |
miRNA | MicroRNA |
BBB | Blood-brain barrier |
CSF | Cerebrospinal fluid |
CNS | Central nervous systems |
CPP | Cell-penetrate peptides |
FBP9R | Fas-blocking peptide with 9R |
CTP9R | Control peptide with 9R |
siFITC | FITC-labeled siRNA |
siCy5 | Cy5-labeled siRNA |
siSOD1 | SOD1-targeting siRNA |
siBax | Bax-targeting siRNA |
siGFP | GFP-targeting siRNA |
siCD4 | CD4-targeting siRNA |
ECA | External carotid artery |
CCA | Common carotid artery |
TTC | 2,3,5-tryphenyltetrazolium chloride |
AFM | Atomic force microscopy |
DLS | Dynamic light scattering |
MFI | Mean fluorescence intensity |
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Chung, K.; Ullah, I.; Yi, Y.; Kang, E.; Yun, G.; Heo, S.; Kim, M.; Chung, S.-E.; Park, S.; Lim, J.; et al. Intranasal Delivery of Anti-Apoptotic siRNA Complexed with Fas-Signaling Blocking Peptides Attenuates Cellular Apoptosis in Brain Ischemia. Pharmaceutics 2024, 16, 290. https://doi.org/10.3390/pharmaceutics16020290
Chung K, Ullah I, Yi Y, Kang E, Yun G, Heo S, Kim M, Chung S-E, Park S, Lim J, et al. Intranasal Delivery of Anti-Apoptotic siRNA Complexed with Fas-Signaling Blocking Peptides Attenuates Cellular Apoptosis in Brain Ischemia. Pharmaceutics. 2024; 16(2):290. https://doi.org/10.3390/pharmaceutics16020290
Chicago/Turabian StyleChung, Kunho, Irfan Ullah, Yujong Yi, Eunhwa Kang, Gyeongju Yun, Seoyoun Heo, Minkyung Kim, Seong-Eun Chung, Seongjun Park, Jaeyeoung Lim, and et al. 2024. "Intranasal Delivery of Anti-Apoptotic siRNA Complexed with Fas-Signaling Blocking Peptides Attenuates Cellular Apoptosis in Brain Ischemia" Pharmaceutics 16, no. 2: 290. https://doi.org/10.3390/pharmaceutics16020290
APA StyleChung, K., Ullah, I., Yi, Y., Kang, E., Yun, G., Heo, S., Kim, M., Chung, S.-E., Park, S., Lim, J., Lee, M., Rhim, T., & Lee, S.-K. (2024). Intranasal Delivery of Anti-Apoptotic siRNA Complexed with Fas-Signaling Blocking Peptides Attenuates Cellular Apoptosis in Brain Ischemia. Pharmaceutics, 16(2), 290. https://doi.org/10.3390/pharmaceutics16020290