宫颈癌细胞靶向化纳米复合物在宫颈癌分子影像学诊断和基因治疗中的应用研究

Cervical cancer (CC) is seriously endangering women 's health. The above situation has highlighted the urgent gene-therapy need for new strategies which could have high targeted gene transfection efficiency in CC and the delivery in vivo could be tracked. In preliminary studies targeting nanocomposites realized very early diagnosis and effective treatment (Hepatology.2015). This study intends to use another acid-sensitive controlled-release carrier, load contrast agent, Folate targeting, and load TBLR1-siRNA gene (Br J Cancer.2014) for efficient CC cell gene therapy and visualization. We have preliminarily confirmed that nano-composite cancer cell has cell-specific gene transfer function and anti-proliferation, and in vivo cell imaging advantages. Our study will develope a MRI and NIRF visible and targeted multifunctional polymeric nano-carrier, not only a highly effective imaging tool for real-time and non-invasive monitoring but also a powerful nanomedicine platform for gene therapy. This project will not only simultaneously achieve tumor-targeted gene therapy and imaging, but also achieve continuous full process monitoring of gene therapy. This study could provide new ideas to promote the development of efficient gene diagnosis and early treatment of cervical cancer.

宫颈癌严重危害妇女健康，基因载体的缺乏限制了基因治疗在宫颈癌中的应用。申请人在前期研究中利用靶向细胞表面蛋白的纳米复合物进行体内研究，实现了对靶细胞的活体示踪和基因治疗(Hepatology.2015)。本课题拟进一步对酸敏胞内控释纳米载体进行宫颈癌靶向化的叶酸修饰，携带申请人前期证实可确切抑制宫颈癌细胞的TBLR1-siRNA(Br J Cancer.2014)，并负载MRI和活体成像造影剂，使基因治疗全程可视化。我们已在预实验中初步证实该纳米复合物具有预期的宫颈癌细胞特异性基因传输、生长抑制、细胞显像及体内低毒性等优点。本研究将肿瘤靶向基因治疗与双标记的显影手段结合起来，有望在高效靶向宫颈癌细胞的基因治疗的同时进行无创分子影像监测，为促进宫颈癌敏感诊断和高效基因治疗手段的临床转化提供新的思路。

宫颈癌严重危害妇女健康，基因载体的缺乏限制了基因治疗在宫颈癌中的应用。本课题对MRI和活体荧光可视化的酸敏胞内控释纳米载体进行宫颈癌靶向化的叶酸修饰，携带TBLR1-siRNA，进行基因治疗。在体内和体外实验研究中证实该纳米复合物具有宫颈癌细胞特异性基因传输、敏感显像、增殖转移抑制、及体内低毒性等性质。本研究证实，将宫颈癌靶向可视化纳米载体，与确切的治疗基因结合起来，可以在无创分子影像监测的前提下，进行高效靶向宫颈癌细胞的基因治疗，为促进宫颈癌敏感诊断和高效基因治疗手段的临床转化提供新的思路。