Inhibition of miR‐155 in MCF‐7 breast cancer cell line by gold nanoparticles functionalized with antagomir and AS1411 aptamer

Abstract

MicroRNAs are key factors for many biological functions. These regulatory molecules affect various gene networks and involve the subsequent signaling pathways. Therefore, disrupting the expression of these molecules is associated with multiple anomalies in the cells and body. One of the most important related abnormalities is the incidence of cancer. Thus, targeting microRNAs (miRNAs) is an effective approach for cancer gene therapy. Various factors are used for this purpose, including the antagomir nucleotide structure. There are some obstacles in the delivery of nucleotide therapeutics to the target cells, however, the use of nanoparticles could partly overcome these defeciencies. On the other hand, targeted delivery of antagomirs using aptamers, reduces nonspecific effects on nontarget cells. Considering the above, in this study, we designed and fabricated a nanocarrier composed of gold nanoparticles (GNPs), antagomir-155, and nucleolin specific aptamer for breast cancer study and therapy. Here, GNPs were synthesized using citrate reduction and were modified by polyA sequences, AS1411 aptamer, and antagomir-155. Attachment of molecules were confirmed using gel electrophoresis, atomic force microscopy imaging and electrochemical test. The specific entry of modified nanoparticles was investigated by fluorescence microscopy. The efficacy of modified nanoparticles was evaluated using a quantitative polymerase chain reaction (q-PCR) for miR-155 and its target gene. Efficient and specific delivery of AuNP-Apt-anti-miR-155 to target cells was confirmed in comparison with the control cell. The q-PCR analysis showed not only a significant decrease in mir-155 levels but also an elevated TP53INP1 mRNA, direct target of miR-155. The proposed structure inhibits proliferation and stimulates apoptosis by increasing the expression of TP53INP1. Our results suggest that AuNP-Apt-anti-miR-155 could be a promising nano constructorfor breast cancer treatment.