期刊
NANOMEDICINE
卷 12, 期 12, 页码 1385-1399出版社
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2017-0023
关键词
blood-brain barrier; drug efflux; functionalization; P-glycoprotein; siRNA; targeted nanoparticles; transferrin-receptor-binding peptide
资金
- European Regional Development Fund through Programa Operacional Factores de Competitividade - COMPETE
- Fundacao para a Ciencia e a Tecnologia (FCT) [UID/BIM/04293/2013]
- North Portugal Regional Operational Programme
- FCT
- Programa Operacional Potencial Humano
- BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences)
- BiotechHealth Doctoral Programme
- FCT [SFRH/BD/99036/2013, SFRH/BD/90404/2012]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/90404/2012, SFRH/BD/99036/2013] Funding Source: FCT
Explore the use of transferrin-receptor peptide-functionalized nanoparticles (NPs) targeting blood-brain barrier (BBB) as siRNA carriers to silence P-glycoprotein (P-gp). Materials & methods: Permeability experiments were assessed through a developed BBB cell-based model; P-gp mRNA expression was evaluated in vitro; rhodamine 123 permeability was assessed after cell monolayer treatment with siRNA NPs. Results: Beyond their ability to improve siRNA permeability through the BBB by twofold, 96-h post-transfection, functionalized polymeric NPs successfully reduced P-gp mRNA expression up to 52%, compared with nonfunctionalized systems. Subsequently, the permeability of rhodamine 123 through the human BBB model increased up to 27%. Conclusion: Developed BBB-targeted NPs induced P-gp downregulation and consequent increase on P-gp substrate permeability, revealing their ability to modulate drug efflux at the BBB.
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