Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment.

Abstract

BACKGROUND:

Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect.

MATERIALS AND METHODS:

The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c. The therapeutic efficacy and related mechanism of micelles were explored based on the in vitro and in vivo active targeting ability and the suppression of MDR, using hepatocellular carcinoma cell line HepG2 as a model.

RESULTS:

The micelle was demonstrated to possess favorable cellular uptake and tumor penetration ability by specifically recognizing the nucleolin in an AS1411 aptamer-dependent manner. Further, the intracellular accumulation of doxorubicin was significantly improved due to the suppression of ABCG2-mediated drug efflux by miR-519c, resulting in the efficient inhibition of tumor growth.

CONCLUSION:

The micelle-mediated co-delivery of doxorubicin and miR-519c provided a promising strategy to obtain ideal anti-cancer efficacy through the active targeting function and the reversion of MDR.

• Authors: Xiao Liang, Yudi Wang, Hui Shi, Mengmeng Dong, Haobo Han, Quanshun Li
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 16 Pg. 2569-2584 ( 2021) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 33833512 (Publication Type: Journal Article)
• Copyright: © 2021 Liang et al.

Chemical References

• AGRO 100
• Antibiotics, Antineoplastic
• Aptamers, Nucleotide
• MIRN519 microRNA, human
• Micelles
• MicroRNAs
• Oligodeoxyribonucleotides
• Phosphoproteins
• RNA-Binding Proteins
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, pharmacology)
• Apoptosis
• Aptamers, Nucleotide (administration & dosage, chemistry)
• Carcinoma, Hepatocellular (genetics, pathology, therapy)
• Cell Cycle
• Cell Movement
• Cell Proliferation
• Doxorubicin (administration & dosage, pharmacology)
• Drug Delivery Systems (methods)
• Drug Resistance, Multiple
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (genetics, pathology, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Micelles
• MicroRNAs (administration & dosage)
• Oligodeoxyribonucleotides (administration & dosage, chemistry)
• Phosphoproteins (antagonists & inhibitors)
• RNA-Binding Proteins (antagonists & inhibitors)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• Nucleolin