Smartly responsive DNA–miRNA hybrids packaged in exosomes for synergistic enhancement of cancer cell apoptosis
Fan Zhang, Albertina N. Isak, Shiqi Yang, Yuchen Song, Lingjie Ren, Chang Feng, Guifang Chen
Abstract
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.