Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Assunto da revista
País de afiliação
Intervalo de ano de publicação
1.
Acta Pharmacol Sin ; 39(2): 261-274, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29388568

RESUMO

Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC50 values of CD20-SA-NPs were reduced to 5.7 and 2.6 µg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg-1·d-1, iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.


Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/uso terapêutico , Melanoma/tratamento farmacológico , Nanopartículas/uso terapêutico , Células-Tronco Neoplásicas/efeitos dos fármacos , Piranos/uso terapêutico , Animais , Antígenos CD20/química , Antineoplásicos/farmacologia , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Aptâmeros de Nucleotídeos/uso terapêutico , Aptâmeros de Nucleotídeos/toxicidade , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Humanos , Lecitinas/química , Lecitinas/metabolismo , Lecitinas/uso terapêutico , Lecitinas/toxicidade , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Polietilenoglicóis/uso terapêutico , Polietilenoglicóis/toxicidade , Piranos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA