光声/超声双模态多功能相变纳米粒定位、评估乳腺癌前哨淋巴结及载药治疗转移淋巴结的研究

The incidence of breast cancer has ranked first in female malignancy. Pathological status of sentinel lymph node (SLN) plays a critical role in staging and treatment for the patients with breast cancer. How to accurately locate SLN, improve detection and accuracy rate are the urgent problems to be sovled in clinic. In this study, a kind of biodegradable polymer material will be employed to synthesise a new multi-functional phase transition nanodroplets as its shells , which will be used in diagnosis, location and treatment of lymph node. Carbon nanoparticles which have a good optical absorption in the near-infrared light and perfluorocarbon will be packaged in the nanodroplets. After laser irradiation, dual-modality contrast imaging of photoacoustic/ultrasound can be achieced due to the phase transition of perfluorocarbon and photoacoustic effect induced by carbon nanoparticles. After subcutaneous injection of the nanodroplets, real-time location and evaluation of SLN can be achieved by photoacoustic imaging and contrast enhanced ultrasonography. SLN stained by the nanodroplets also can be clearly identified with naked eyes in surgery. The multi-functional nanodroplets have the ability of encapsulating chemotherapy drugs. The photothermal effect induced by nanodroplets can damage tumor cells, moreover, the released chemotherapy drugs also can synergistically damage tumor cells. A new method will be provided to accurately locate, evaluate SLN of breast cancer and precisely treat metastatic lymph node.

乳腺癌发病率已高居女性恶性肿瘤的首位。前哨淋巴结(SLN)是否转移对乳腺癌分期、指导治疗及预后判断均具有十分重要的临床意义。如何精确定位SLN、提高前哨淋巴结活检的检出率与准确性是目前临床急需解决的关键难题之一。本研究结合分子影像学研究进展，采用高分子生物可降解材料构建一种集诊断、定位与治疗于一体的新型多功能相变纳米粒，该纳米粒包裹在近红外光有良好光学吸收属性的纳米炭染料及相变材料液态氟碳，经激光辐照后，通过纳米炭的光声效应和液态氟碳的液气相变可实现光声/超声双模态对比显影。皮下注射该纳米粒后，可通过光声及超声显像实时精确定位和评估SLN，术中肉眼亦能清楚辨认染色的SLN。该多功能纳米粒还可包载化疗药物，结合光致相变技术，使纳米粒在淋巴结内发生液气相变并产生光热效应，杀伤肿瘤细胞的同时释放化疗药物产生协同治疗作用，为乳腺癌SLN精确定位与评估及转移淋巴结精准治疗提供一种新的方法。

乳腺癌发病率已高居女性恶性肿瘤的首位。乳腺癌患者前哨淋巴结(SLN)是否转移对乳腺癌分期、指导治疗及预后判断均具有十分重要的临床意义。精确定位SLN、提高前哨淋巴结活检的检出率与准确性以及对转移淋巴结的治疗是目前临床急需解决的关键难题之一。本研究结合分子影像学研究进展，构建及制备了一种集诊断、定位与治疗于一体的新型多功能纳米粒（以生物可降解材料PLAG为外壳，其内载纳米炭、液态氟碳及紫杉醇），在原设计基础上，进一步制备了载HIF-1ɑ单抗的靶向纳米粒。该纳米粒主要用于淋巴结的双模态显影、光热治疗及药物的递送。该纳米粒经体内外检测，具有大小均一合适、吸光性好、生物安全性好、载药量高、靶向性好等优点。该纳米粒在体内/外经激光辐照后，可产生光声效应，实现光声显影；同时，纳米炭吸光后，产生光热效应，使其内的液态氟碳发生液气相变，实现超声显影。皮下注射该纳米粒，纳米粒被动靶向达到淋巴结，通过激光辐照淋巴结实现光声/超声双模态对比显影，进行精确诊断及定位，与此同时，切开后肉眼下亦能清楚辨认黑染的SLN，有利于SLN的手术活检。该多功能纳米粒还可包载化疗药物，本研究包载了乳腺癌治疗的一线化疗药物紫杉醇，通过纳米粒淋巴结靶向性到达淋巴结内（在载IF-1α单抗后实现主动和被动双靶向），经激光辐照后，纳米粒在转移淋巴结内发生液气相变并产生光热效应，破坏肿瘤细胞的同时释放化疗药物紫杉醇，产生光热治疗与化疗的协同作用，为乳腺癌转移淋巴结提供一种新的治疗方法。