Smartly responsive DNA-miRNA hybrids packaged in exosomes for synergistic enhancement of cancer cell apoptosis

Endogenous and exogenous tumor-related microRNAs (miRNAs) are considered promising tumor biomarkers and tumor therapeutic agents. In this work, we propose a miRNA self-responsive drug delivery system (miR-SR DDS), which enables the association between endogenous and exogenous miRNAs, so as to achiev...

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Bibliographic Details
Published in:Nanoscale 2022-05, Vol.14 (17), p.6612-6619
Main Authors: Zhang, Fan, Isak, Albertina N, Yang, Shiqi, Song, Yuchen, Ren, Lingjie, Feng, Chang, Chen, Guifang
Format: Article
Language:English
Subjects:
Apoptosis
Biomarkers
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cell Line, Tumor
Cell Movement
Cell Proliferation
Chemical compounds
Deoxyribonucleic acid
DNA
DNA, Complementary - metabolism
Drug delivery systems
Exosomes - metabolism
Female
Gene expression
Gene Expression Regulation, Neoplastic
Humans
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Pharmacology
Tumors
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Summary:Endogenous and exogenous tumor-related microRNAs (miRNAs) are considered promising tumor biomarkers and tumor therapeutic agents. In this work, we propose a miRNA self-responsive drug delivery system (miR-SR DDS), which enables the association between endogenous and exogenous miRNAs, so as to achieve a smart responsive and synergistic drug delivery. The miR-SR DDS consists of DNA-miRNA hybrids of let-7a and the complementary DNA of miR-155, which was packaged in exosomes. In response to the overexpressed miR-155 in breast cancer cells, the hybrids disintegrate and release let-7a and the complementary DNA of miR-155 to inhibit the expression of HMGA1 and relieve the inhibition of SOX1, respectively. Under the dual-targeted gene regulation, results show that the growth, migration and invasion of breast cancer cells can be synergistically inhibited through the Wnt/β-catenin signaling pathway. The concept and successful practice of the miR-SR DDS can be used as a reference for the development of miRNA drugs. We associate endogenous and exogenous miRNAs to achieve a smart response and a coordinated drug delivery system.
ISSN:2040-3364
2040-3372
DOI:10.1039/d1nr08539e