A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA

作者：Hwang Do Won; Son Sejin; Jang Jaeho; Youn Hyewon; Lee Song; Lee Duhwan; Lee Yun Sang; Jeong Jae Min; Kim Won Jong; Lee Dong Soo

来源：Biomaterials, 2011, 32(21): 4968-4975.

DOI：10.1016/j.biomaterials.2011.03.047

• MicroRNA
• RVG peptide
• PEI polymer
• Brain-targeting agent
• Polyplex

Recent advances in efficient microRNA (miRNA) delivery techniques using brain-targeted nanoparticles offer critical information for understanding the functional role of miRNAs in vivo, and for supporting targeted gene therapy in terms of treating miRNA-associated neurological diseases. Here, we report the rabies virus glycoprotein (RVG)-labeled non-toxic SSPEI nanomaterials capable of neuron-specific miR-124a delivery to neuron in vivo. The RVG-labeled BPEI-SS (RVG-SSPEI) nanocarrier showed less toxicity in acetylcholine receptor-positive Neuro2a cells, and electrostatic interaction of RVG-SSPEI with miR-124a exhibited optimal transfection efficacy. The RVG-SSPEI polymer specifically targeted Neuro2a using cy5.5-miR-124a mixed with RVG-SSPEI. The functional action of miR-124a oligomers released from polyplexes in the cytoplasmic region was evaluated by a reporter vector containing a miR-124a -binding sequence, and showed a significantly reduced reporter signal in a dose-dependent manner. Cy5.5-miR-124a/RVG-SSPEI- injected into mice via tail veins displayed the enhanced accumulation of miR-124a in the isolated brain. Hindrance of the efficient penetration of neuronal cells by size limitation of the miR-124a/RVG-SSPEI improved with the help of mannitol through blood-brain barrier disruption. These findings indicated that the RVG peptide combined with mannitol infusion using SSPEI polymer for neuron-specific targeting in vivo is sufficient to deliver neurogenic microRNA into the brain.

• 出版日期2011-7