乳腺癌早期诊断与靶向治疗一直是现代医学前沿热点与难点，分子影像学的快速发展有望使这一重大研究课题取得突破，而多功能诊疗一体化分子探针是实现肿瘤靶向分子显像及可视化精准治疗的重要基础。本课题基于前期相关重要研究成果，针对乳腺肿瘤微酸性环境特点，采用自主装与原位矿化技术，研制一种装载CaCO3和血卟啉的PEG-PASP纳米探针，该智能型多功能探针可通过EPR效应聚集于乳腺肿瘤部位，在弱酸性环境下探针被“激活”产生CO2定位增强肿瘤超声显像。同时，探针上特有的腙键在弱酸性环境下断裂水解，显露其含有的功能性多肽并特异性与乳腺癌细胞表面受体结合，随后介导载血卟啉的纳米粒主动转运入癌细胞内，实现pH控制的连锁靶向超声显像及药物定位递送。进而，基于卟啉类物质良好的光声效应及光/声动力治疗特性，利用光声成像技术行肿瘤细胞内显像，同时激活血卟啉产生定位杀伤效果，实现乳腺癌靶向显像与可控性可视化精准治疗。

Early diagnosis and targeted treatment of breast cancer has been the hot and difficult field of forefront research in modern medical science, the rapid development of molecular imaging is expected to make this important research breakthroughs, and multi-functional molecular probes are the potential candidates to achieve the integration of tumor targeted molecular imaging and for accurate visualized therapy. Based on our preliminary important findings related to this research, to realize the slightly acidic environment in breast tumor tissue characteristics, we prepare a novel nanoprobe loading CaCO3 and hematoporphyrin using the self-assembly and in situ mineralization technology. The smart multifunction probe could accumulate at the breast tumor site through the EPR effect, the probes are then "active" in the acidic environment of tumor, as a result, CaCO3 generate CO2 gas enhancing tumor targeting ultrasound imaging. At the same time, the specific hydrazone bond of the probe fracture and hydrolysis in the acidic environment, revealing the functional polypeptide so the peptide could specifically bind to the receptors existing on the breast tumor cell surface, and then mediated hematoporphyrin actively transport into tumor cells. The whole process is pH-controlled series effects including tumor targeted ultrasound imaging and cell targeted drug delivery. Furthermore, based on good photoacoustic effect and photodynamic/sonodynamic characteristics of porphyrins, hematoporphyrin can be used for tumor cell photoacoustic imaging, while activating hematoporphyrin could generate tumor targeted killing effect. In a word, the smart nanoprobe could achieve pH-controlled breast tumor targeting imaging and accurate visualized therapy.