Oral cancer represents the sixth most frequent cancer in the world, characterized by high poor prognosis and low survival rate due to local relapse and metastasis. MicroRNAs (miRNAs) have been discovered as diagnostic biomarkers and therapeutic targets for oral cancer. However, one of the major challenges of miRNAs-based theranostical approach is to achieve efficient and safe delivery. Thus, a reliable sensing strategy that can detect miRNAs expression levels in living cancer cells is urgently needed. Herein, a novel sensing platform based on nanoscale metal-organic framework (NMOF) conjugated with the fluorophores-labeled single-stranded DNA probe (p-DNA) was fabricated to monitor and inhibit multiplexed miRNAs expression in living oral cancer cells. The flow cytometry and confocal laser scanning microscopy (CLSM) were carried out to evaluate the expression levels of miRNAs in oral cancer cells. The miRNA inhibition efficiency was examined by RT-PCR. The effects of the complexes on tumor cell invasion and migration were assessed by transwell assay and wound healing. The flow cytometry, colony formation assay and CCK8 were used to assess cell apoptosis and proliferation. The results showed that NMOF works as fluorescence quencher of the labeled p-DNA. In presence of the target miRNA (including miR-7, miR-21, and miR-155), p-DNA was able to rapidly hybridize and release from the NMOF leading to the recovery of fluorescence in living cells, which can be detected in real-time. Moreover, RT-PCR results demonstrated that the multiplexed miRNAs could be effectively downregulated after treatment of p-DNA@NMOF, resulting in the simultaneous suppression of oral cancer cell proliferation, anti-apoptosis, migration and invasion in vitro. In summary, our study suggests that p-DNA@NMOF possess great potential for combining early diagnosis and gene therapy of oral cancer.

Note: This abstract was not presented at the meeting.

Citation Format: Pei Yu, Zehang Zhuang, Guihua Qiu, Haolin Chen, Yuying Zhao, Jinxiang Chen, Xiqiang Liu. Theranostical nanoscale metal-organic frameworks-mediated rapid multiplexed microRNA detection and highly therapeutic efficacy in living oral cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2190. doi:10.1158/1538-7445.AM2017-2190