乳腺癌是分子水平上高度异质型的疾病，以精准诊断为基础的个体化治疗可以有效提高治愈率，降低复发率。开发实时动态分子影像诊疗一体化制剂是推动其广泛应用的关键。本项目拟通过基因工程技术在趋磁细菌中生产一种对乳腺癌具有分子靶向、双模成像和治疗功能的生物纳米磁小体诊疗探针。最新研究发现，生物相容性高、容易降解的生物纳米磁小体可以用于MR成像和肿瘤热疗，而iRFP蛋白和纳米抗体分别适用于近红外成像和肿瘤的靶向治疗。因此，利用基因修饰的趋磁细菌生产表面展示乳腺癌靶向治疗功能的纳米抗体和近红外荧光蛋白的纳米磁小体探针，可以实现对肿瘤的分子靶向双模成像和治疗。探针注射后，通过MR和近红外成像检测其在肿瘤和体内的分布规律，揭示乳腺癌的分子表型。探针表面的纳米抗体和交变磁场的下热疗作用可以有效抑制肿瘤的生长。本项目对研发诊疗一体化制剂，发展乳腺癌分子影像和促进个体化治疗方案的临床转化具有重要意义。

Breast cancer is highly heterogeneous disease at molecular level. Accurate diagnosis greatly benefits individualized treatment with increasing patient curable rate and reducing relapse rate. Investigating real time dynamic imaging and treatment agent of breast cancer will be very helpful to the development of individualized treatment. This project aims to employ magnetosome of magnetotactic bacterium to develop an theranostic probe with the ability of dual-model imaging, targeting specific biomarker of breast cancer and inhibiting its growth through gene technology. The current researches indicate that magnetosome of highly biocompatibility and biodegradation can be used as contrast agent of MRI while iRFP and nanobody are qualified for near-infrared imaging and tumor-targeting therapy, respectively. Therefore, using gene modified magnetotactic bacterium to produce magnetosome probe, on the surface of which breast cancer targeting and treatment nanobody and near-infrared protein will be displayed. This probe could be used as tumor-targeting dual-model imaging and treatment. After injection of the probe, MRI and near-infrared imaging could detect its distribution in tumor and other parts of the body, and reveal molecular phenotypes of breast cancer. Depending on accumulation of the probe in breast cancer, nanobody on the surface of the probe and its hyperthermia therapy under alternating magnetic field will efficiently inhibit the growth of tumor. This work will greatly contribute to developing theranostic and molecular imaging agent of breast cancer and promoting the clinical application of individualized treatment.