Gomes Maria João, Kennedy Patrick J, Martins Susana, Sarmento Bruno
i3S, Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
INEB, Instituto de Engenharia Biomédica, Biocarrier Group, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
Nanomedicine (Lond). 2017 Jun;12(12):1385-1399. doi: 10.2217/nnm-2017-0023. Epub 2017 May 19.
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.
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%.
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.
探索将转铁蛋白受体肽功能化的纳米颗粒（NPs）作为小干扰RNA（siRNA）载体靶向血脑屏障（BBB）以沉默P-糖蛋白（P-gp）的应用。
通过建立的基于BBB细胞的模型评估通透性实验；在体外评估P-gp mRNA表达；在用siRNA NPs处理细胞单层后评估罗丹明123的通透性。
转染96小时后，功能化的聚合物纳米颗粒除了能够将siRNA透过血脑屏障的通透性提高两倍外，与未功能化的系统相比，还成功地将P-gp mRNA表达降低了52%。随后，罗丹明123透过人血脑屏障模型的通透性提高了27%。
所开发的靶向血脑屏障的纳米颗粒诱导P-gp下调，从而导致P-gp底物通透性增加，揭示了它们调节血脑屏障处药物外排的能力。
