基于氧化钽纳米结构的酸热双敏感的靶向纳米材料用于癌症诊疗的研究

Lung cancer is the first most common cancer for death rate in the world. In clinic, the most common cancer treatments include surgery, radiotherapy and chemotherapy. During the surgery, the doctor usually do not know where is the margin of the tumor, which is easy to result that the tumor resection is not clean or excessive. And the main problem of radiotherapy and chemotherapy is that the drug or radiation without specificity could cause damage to the normal tissues. To overcome these problems, based on our preliminary data, we aim to synthesize a small library of EGFR antibody and EGFR mutation small molecules conjugated tantalum oxide-based core-shell nanoparticle for pH/thermal sensitive multifunctional agents for lung cancer theranostic. Their targeting properties will be studied in vitro through flow cytometry and their biodistribution in vivo will be detected through small animal imaging equipments to further confirm their targeting properties. Combine the advantages of multimodal imaging modalities, the diagnostic efficiency will be improved and the tumor margin will be accurately judged. The pH/thermal sensitive properties of the nanoparticles will be help to the controllable and topical cancer therapy. In summary, tantalum oxide based nanoparticles will be a prospective integrated probe in the early detection and controllable therapy of cancer, which can improve the therapeutic efficiency of lung cancer.

恶性肿瘤中肺癌的死亡率居世界首位。在临床上，对于肿瘤患者的治疗方式一般是通过手术切除和放化疗，手术中医生根本就不知道癌组织与健康组织的界限在哪里，很容易造成肿瘤切除不干净或过度切除，而放化疗存在的主要问题是药物不具备特异性易损伤正常组织。为了克服这些问题，本项目基于前期研究基础，以表皮生长因子受体（突变和不突变两种）为靶点，拟合成一系列基于氧化钽纳米结构的酸-热双敏感的肺癌靶向的多模态纳米探针，进一步通过流式细胞仪在细胞水平研究其细胞靶向性，通过小动物成像设备在动物水平研究其肿瘤靶向性及体内分布情况。多种影像学手段优势互补，实现肺部肿瘤边界的准备判定。酸热双敏感的特性易于实现化疗药物在肿瘤局部快速释放，有利于实现肿瘤的可控化/热疗。这将为肺癌的早期发现和可控治疗提供新型的诊疗一体化探针，有利于肺癌治疗效率的显著提供。