乳腺癌早期特异性诊断及疗效增敏对于临床乳腺癌的诊疗具有重要意义。我们前期研究表明，依赖于距离可调控的纳米分子探针在肿瘤高还原状态（GSH）下可实现T1-T2双激活，从而有效提高了肿瘤诊断的敏感性，但该探针对微小肿瘤的反应性低，同时T1-T2激活后对超微肿瘤检测缺乏敏感性。针对以上问题，本项目拟构建能够在肿瘤酸性微环境下T1-T2特异性激活含免疫佐剂R837的新型pH敏感纳米探针，并联合双对比增强减影技术（DESI）增强肿瘤-正常组织的信号比，实现超微肿瘤高敏感性及特异性检出。另外，该新型纳米载药分子探针能够在光热激发下使机体产生“疫苗”效应实现免疫治疗增敏。此项目的顺利实施，将有助于乳腺癌的早期特异性诊断，并为乳腺癌的免疫治疗增敏提供新思路，从而为临床上乳腺癌新型诊疗方案的开发提供重要理论依据。

Early specific diagnosis and therapeutic sensitization of breast cancer are of great significance for the breast cancer diagnosis and treatment in clinical practice. Our preliminary data have shown that T1-T2 double activation can be achieved under the high-reduction state (GSH) of tumor by molecular distance controllable nano-molecular probes, which can effectively improve the sensitivity of tumor diagnosis, however, low reactivity was found on this probe to micro-tumors and lacking of ability to ultra-small tumor detection activity after T1-T2 activation. In response to the above problems, this project aims to construct a novel pH-sensitive nanoprobe containing immunological adjuvant R837 that can specifically activate T1-T2 signal intensity under the acidic microenvironment of tumor, moreover, the enhanced tumour-to-normal-tissue signal ratio could be achieved by combining the double contrast enhanced subtraction technique (DESI), thereby achieving the sensitivity and specificity of detection of ultra-small tumors. In addition, the novel nano drug-loaded molecular probe can also produce a "vaccine" effect under the photothermal excitation to achieve immunotherapy sensitization. The successful implementation of this project will be helpful for the early specific diagnosis of breast cancer and provide new ideas for the sensitization of breast cancer immunotherapy, thus providing an important theoretical basis for the development of clinical new breast cancer treatment programs.