摘要
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 mi RNA(let-7 i)(Cy5-mi RNA) 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(SKOV3 DDP cells). The Cy5-mi RNA adsorbed on NGO could selectively bind the drug resistance related m RNA follow by suppress the expression of drug resistance m RNA, and the binding simultaneously induced the release of Cy5-mi RNA from the NGO, thus the fluorescence signal of Cy5 recovered and could be used for drug resistance monitoring.Moreover, the mi RNA 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.
基金
supported by the Huxiang Young Talent Program of Hunan Province (No.2018RS3005)
the InnovationDriven Project of Central South University (No.2020CX048)
the Changsha Science and Technology Plan Project (Nos.kq2005001,kq2004086)
the National Natural Science Foundation of China (No.81301258)
the Natural Science Foundation of Hunan Province (Nos.2019JJ60071,2020JJ4680)
the Shenghua Yuying Project of Central South University,the Hunan Provincial Graduate Research and Innovation Project (No.CX20190242)
National College Students’ Innovation and Entrepreneurship Training Program (Nos.S2020105330414,S202010533015X,8304180412)
the Postgraduate Innovation Project of Central South University (Nos.2020zzts819,2020zzts408,2020zzts409,2021zzts0977,2021zzts0979)
the Open-End Fund for the Valuable and Precision Instruments of Central South University。