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Delivery of Liver-Specific miRNA-122 Using a Targeted Macromolecular Prodrug toward Synergistic Therapy for Hepatocellular Carcinoma.
ACS Appl Mater Interfaces ; 11(11): 10578-10588, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30802029
ABSTRACT
Hepatocellular carcinoma (HCC) poses a great threat to human health. The elegant combination of gene therapy and chemotherapy by nanocarriers has been repeatedly highlighted to realize enhanced therapeutic efficacy relative to monotreatment. However, the leading strategy to achieve the efficient codelivery of the gene and drug remains the electrostatic condensation with the nucleic acid and the hydrophobic encapsulation of drug molecules by the nanocarriers, which suffers substantially from premature drug leakage during circulation and severe off-target-associated side effects. To address these issues, we reported in this study the codelivery of liver-specific miRNA-122 and anti-cancer drug 5-fluorouracil (5-Fu) using a macromolecular prodrug approach, that is, electrostatic condensation with miRNA-122 using galactosylated-chitosan-5-fluorouracil (GC-FU). The delivery efficacy was evaluated comprehensively in vitro and in vivo. Specifically, the biocompatibility of GC-FU/miR-122 nanoparticles (NPs) was assessed by hemolysis activity analysis, BSA adsorption test, and cell viability assay in both normal liver cells (L02 cells) and endothelial cells. The resulting codelivery systems showed enhanced blood and salt stability, efficient proliferation inhibition of HCC cells, and further induction apoptosis of HCC cells, as well as downregulated expression of ADAM17 and Bcl-2. The strategy developed herein is thus a highly promising platform for an effective codelivery of miRNA-122 and 5-Fu with facile fabrication and great potential for the clinical translation toward HCC synergistic therapy.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Materiais Biocompatíveis / Pró-Fármacos / MicroRNAs Aspecto clínico: Terapia Limite: Animais / Humanos Idioma: Inglês Revista: ACS Appl Mater Interfaces Assunto da revista: Biotecnologia / Engenharia Biomédica Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: China