Engineered exosomes loaded with miR-449a selectively inhibit the growth of homologous non-small cell lung cancer

Wen Zhou,Mingjun Yang,Zhipeng Wang,Mingming Xu

doi:10.1186/s12935-021-02157-7

Wen Zhou, Mingjun Yang + Show 2 more

Open Access

https://doi.org/10.1186/s12935-021-02157-7

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Abstract

As an efficient drug carrier, exosome has been widely used in the delivery of genetic drugs, chemotherapeutic drugs, and anti-inflammatory drugs. As a genetic drug carrier, exosomes are beneficial to improve transfection efficiency and weaken side effects at the same time. Here, we use genetic engineering to prepare engineered exosomes (miR-449a Exo) that can actively deliver miR-449a. It was verified that miR-449a Exo had good homology targeting capacity and was specifically taken up by A549 cells. Moreover, miR-449a Exo had high delivery efficiency of miR-449a in vitro and in vivo. We demonstrated that miR-449a Exo effectively inhibited the proliferation of A549 cells and promoted their apoptosis. In addition, miR-449a Exo was found to control the progression of mouse tumors and prolong their survival in vivo. Our research provides new ideas for exosomes to efficiently and actively load gene drugs, and finds promising methods for the treatment of non-small cell lung cancer.

Highlights

Lung cancer is one of the most common malignant tumors with the highest incidence and fatality rate in the world [1]
One plasmid contained the membrane localization protein ADC linked to the transactivator protein (TAT) peptide, and the other contained the miR-449a precursor linked to the trans-activating response (TAR) element
The results showed that the surfaces of unload Exo and miR-449a Exo both highly expressed CD63 and CD9, while CD63 and CD9 on the surface of A549 cell membrane showed low expression (Fig. 1C)

Summary

Introduction

Lung cancer is one of the most common malignant tumors with the highest incidence and fatality rate in the world [1]. Most NSCLC patients have developed to advanced stages at the time of Recently, increasing attention has been attached to the relationship between miRNA and NSCLC. MiRNA cleaves mRNA or inhibits translation initiation by imprecisely complementary pairing with the 3′-untranslated region (UTR) of mRNA [5]. It regulates cell differentiation, proliferation, apoptosis, carcinogenesis, hormone secretion and many other biological processes. Many studies have found that there are a variety of miRNA expression disorders in tumor tissues, and these miRNAs may participate in the occurrence and development of tumors by regulating the expression of genes related to cell malignant phenotype [6]. In NSCLC cells or tissues, miR-21 [7], miR-574-5p [8], miR-26 [9], miR-155 [10], miR-1254 [11], miR-449a [12] and other miRNAs

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