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1.
Adv Healthc Mater ; 8(5): e1801358, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30672150

RESUMO

There is currently no cure for gene mutation-caused autosomal dominant polycystic kidney disease (ADPKD). Over half of patients with ADPKD eventually develop kidney failure, requiring dialysis or kidney transplantation. Current treatment modalities for ADPKD focus on reducing morbidity and mortality from renal and extrarenal complications of the disease. MicroRNA has been shown to be useful in treating ADPKD. This study combines anti-miRNA plasmids and iron oxide/alginate nanoparticles for conjugation with antikidney antibodies. These nanocomposites can specifically target renal tubular cells, providing a potential treatment for ADPKD. Magnetic resonance imaging and in vivo imaging system results show effective targeting of renal cells. Anti-miRNA plasmids released from the nanocomposites inhibit cell proliferation and cyst formation in the PKD cellular and animal models. The results suggest the novel combination of the anti-miRNA plasmids and nanomaterials provides potential clinical implications for ADPKD treatment.


Assuntos
MicroRNAs/administração & dosagem , Nanocompostos/administração & dosagem , Nanocompostos/química , Plasmídeos/administração & dosagem , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/terapia , Animais , Linhagem Celular , Rim/patologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Plasmídeos/genética
2.
Int J Nanomedicine ; 14: 9665-9675, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824158

RESUMO

PURPOSE: Vitamin D is a novel potential therapeutic agent for peritoneal dialysis (PD)-related peritoneal fibrosis, but it can induce hypercalcemia and vascular calcification, which limits its applicability. In this study, we create nanotechnology-based drug delivery systems to investigate its therapeutics and side effects. MATERIALS AND METHODS: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino-(polyethylene glycol)2000] (DSPE-PEG) and L-α-phosphatidylcholine (PC), which packages with 1α,25(OH)2D3, were used to construct vitamin D nanoliposomes. To confirm the function and safety of vitamin D nanoliposomes, peritoneal mesothelial cells were treated with TGF-ß1 and the reverse was attempted using vitamin D nanoliposomes. Antibodies (Ab) against the peritoneum-glycoprotein M6A (GPM6A) Ab were conjugated with vitamin D nanoliposomes. These particles were implanted into mice by intraperitoneal injection and the animals were monitored for the distribution and side effects induced by vitamin D. RESULTS: Vitamin D nanoliposomes were taken up by the mesothelial cells over time without cell toxicity and it also provided the same therapeutic effect in vitro. In vivo study, fluorescent imaging showed vitamin D nanoliposomes allow specific peritoneum target effect and also ameliorate vitamin D side effect. CONCLUSION: Nanoliposomes vitamin D delivery systems for the prevention of PD-related peritoneal damage may be a potential clinical strategy in the future.


Assuntos
Nanomedicina , Diálise Peritoneal/efeitos adversos , Peritônio/patologia , Vitamina D/farmacologia , Animais , Anticorpos/farmacologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Liberação Controlada de Fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Cinética , Lipossomos , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Peritônio/efeitos dos fármacos , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Fator de Crescimento Transformador beta1/metabolismo
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