Personalized nanomedicine for the treatment of vascular hypertension in polycystic kidney disease models

摘要

In our current study,we designed a nanomedical device for the treatment of vascular hypertension in polycystic kidney disease(PKD)model through cilia targeting.We generated and compared two different metal and polymer cilia-targeted nanoparticle drug delivery systems(DDS),i.e.gold(Au)and poly-actic-co-glycolic acid(PLGA)nanoparticles(NPs).These DDS were targeted to dopamine-receptor type-5(DR5)on primary cilia and also loaded with fenoldopam(FD).The structures and sizes of the DDS were visualized with transmission electron microscopy(TEM).The size of the DDS was also confirmed with the dynamic light scattering.The diameters of Au-NPs and PLGA-NPs were approximately 40±2.5 and 102±4.8 nm,respectively.The surface charge of Au-NPs(-47.3 ± 1.2 mV)was significantly more negative than PLGA-NPs(-25.9 ± 1.0 mV).Fourier transform infrared spectroscopy(FTIR)also confirmed the conjugation of DR5 antibody with both DDS.Our in vivo studies reveal that both DDS showed improved blood pressure in PKD mice through NO mediated vasodilation.