Let‐7i miRNA and platinum loaded nano‐graphene oxide platform for detection/reversion of drug resistance and synergetic chemical‐photothermal inhibition of cancer cell

Abstract

The drug resistance of chemotherapy is a major challenge to overcome for antineoplastic agents and the reverse of drug resistant is essential for cancer therapy. Herein, we developed a drug delivery system which can simultaneously detect/reverse the drug resistance and perform synergetic treatment of cancer. In this work, we integrated cyanine5 (Cy5) modified miRNA (let-7i) (Cy5-miRNA) and platinum onto nano-graphene oxide (NGO) (30-50 nm) platform to achieve simultaneously detection/reversion of drug resistance and synergetic treatment of cisplatin resistant SKOV3 cells (SKOV3DDP cells). The Cy5-miRNA adsorbed on NGO could selectively bind the drug resistance related mRNA follow by suppress the expression of drug resistance mRNA, and the binding simultaneously induced the release of Cy5-miRNA from the NGO, thus the fluorescence signal of Cy5 recovered and could be used for drug resistance monitoring. Moreover, the miRNA suppressed the Cyclin D1 protein expressions thus reversed the drug resistance. The loaded platinum(IV) (Pt(IV)) was converted to the therapeutic platinum(II) (Pt(II)) in both tumor acidic and reductive environment responsive behavior. NGO furtherly performed photothermal therapy under near infrared (NIR) laser irradiation and enhanced the therapeutic effect. All in all, this nanoplatform realized detection/reversion of the drug resistance as well as synergetic chemical-photothermal treatment of ovarian cancer cells, which holds great promise in the treatment of drug resistant cancer cells.