核酸功能化聚多巴胺纳米探针在miRNA响应的肿瘤成像与治疗中的应用研究

Cancer is a serious threat to human health. Early diagnosis and early treatment of cancer is crucial for prolong the long-term survival and improve the curative possibility. Abnormal expression of specific miRNAs was closely associated with the carcinogenesis and development of different cancers, thus miRNA has been identified as new diagnostic and prognostic biomarkers for cancer, as well as provide new strategies for cancer treatment. Focusing on the clinical demands of cancer early diagnosis and treatment, we will construct a new nucleic acid nanoprobe platform by using polydopamine nanoparticle and the multifunctional nucleic acid probes. This type of probe can simultaneously target to cancer tissue, image intracellularly abnormal expressed miRNAs and block the cancer promoting related functions, and thus to integrate the cancer diagnosis and treatment together. In addition, we will also develop novel signal amplification strategies based on nucleic acid self-assembly at cellular level to specifically image the cancer-related miRNA with low abundance, and thus improve the sensitivity and specificity of cancer early diagnosis and prognosis. Overall, this study might provide novel ideas for developing new strategies for caner early diagnosis and treatment.

癌症严重威胁人类生命健康，实现癌症的早期诊断与治疗对于延长患者生存时间、提高治愈率具有非常重要的意义。其中，miRNA的异常表达与癌症的发生发展密切相关，有望作为癌症诊断和预后监测的新指标，也能够为癌症治疗提供新思路。本项目从癌症早期诊断与治疗这一临床需求出发，利用聚多巴胺纳米颗粒与多功能核酸构建一种新型核酸纳米探针。该探针能够靶向进入癌细胞，荧光成像癌细胞内过表达的miRNA并抑制其参与的调控作用，从而实现诊疗一体化。此外，构建基于核酸之间自组装的细胞水平的成像信号放大方法，实现癌细胞内低丰度癌症相关miRNA的特异性成像，从而提高癌症早期诊断与预后监测的灵敏度。本研究有望为癌症患者的早期诊断与治疗提供新的思路。

癌症的早期诊断与治疗对于延长患者生存时间、提高治愈率具有非常重要的意义。肿瘤微环境对肿瘤的发生、发展和转移起着重要作用。肿瘤内的癌细胞具有明显异质性，但肿瘤微环境相对比较稳定，具有乏氧、还原环境等特征。对肿瘤和肿瘤微环境进行深入研究具有重要理论意义与应用前景。本项目利用聚多巴胺辅助构建核酸功能化纳米探针并实现癌症相关microRNA特异响应的荧光成像与治疗。该探针无需转染试剂就能进入癌细胞，通过荧光恢复来成像癌细胞内的目标microRNA，并与纳米材料的光热治疗相结合实现成像与治疗功能一体化。此外，构建几种能够特异性响应肿瘤微环境相关因素的荧光成像探针，从而进行肿瘤微环境的分析与监测。本项目希望能为癌症研究和诊断治疗提供新的思路和手段。