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J Nanobiotechnology ; 17(1): 125, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870362

RESUMO

BACKGROUND: Multidrug resistance (MDR) is a pressing obstacle in clinical chemotherapy for breast cancer. Based on the fact that the drug efflux is an important factor in MDR, we designed a codelivery system to guide the drug efflux inhibitor verapamil (VRP) and the chemotherapeutic agent novantrone (NVT) synergistically into breast cancer cells to reverse MDR. RESULTS: This co-delivery system consists of following components: the active targeting peptide RGD, an inorganic calcium phosphate (CaP) shell and an organic inner core. VRP and NVT were loaded into CaP shell and phosphatidylserine polyethylene glycol (PS-PEG) core of nanoparticles (NPs) separately to obtain NVT- and VRP-loaded NPs (NV@CaP-RGD). These codelivered NPs allowed VRP to prevent the efflux of NVT from breast cancer cells by competitively combining with drug efflux pumps. Additionally, NV@CaP-RGD was effectively internalized into breast cancer cells by precise delivery through the effects of the active targeting peptides RGD and EPR. The pH-triggered profile of CaP was also able to assist the NPs to successfully escape from lysosomes, leading to a greatly increased effective intracellular drug concentration. CONCLUSION: The concurrent administration of VRP and NVT by organic/inorganic NPs is a promising therapeutic approach to reverse MDR in breast cancer.


Assuntos
Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Mitoxantrona/química , Nanocápsulas/química , Verapamil/química , Animais , Fosfatos de Cálcio/química , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Sobrevivência Celular , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Quimioterapia Combinada/métodos , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitoxantrona/farmacologia , Terapia de Alvo Molecular , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Fosfatidilserinas/química , Polietilenoglicóis/química , Verapamil/metabolismo
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