包裹光吸收子的、载药相变型光声/超声分子探针靶向多模态显像与治疗视网膜母细胞瘤研究

微泡造影剂用于肿瘤分子显像存在致命缺点，其粒径为微米级、不能穿过血管内皮间隙实现靶向肿瘤细胞显影。纳米级液态氟碳纳米粒可穿过血管内皮间隙靶向肿瘤细胞，但其超声显影能力差，且无法通过超声空化效应实现控释药物。我们前期实验证实，脉冲激光能触发含印度墨水光吸收子的液态氟碳微球（PFH）相变，合理利用其光声效应，对肿瘤能达到显像和治疗的目的。视网膜母细胞瘤（RB）是婴幼儿最常见的眼内恶性肿瘤，缺乏早期诊断方法及有效治疗手段。结合激光被广泛用于治疗视网膜病变，本课题拟制备以RB细胞叶酸受体为靶点、以全氟戊烷（PFP）为核心、载阿霉素（ADM）及光吸收子吲哚菁绿（ICG）、脂质包裹的、具有液气相变能力的光声/超声分子探针，使其靶向聚集于RB细胞；通过脉冲激光辐照，促使其在肿瘤区域相变，产生微气泡及光声效应，靶向释放所载化疗药物ADM，使光声治疗与化疗相结合，减轻全身毒副作用，实现RB的光声/超声双模态显像。

When microbubble contrast agents used for molecular imaging of tumor, there exist a fatal disadvantage, such as it cannot pass through the vascular endothelial gap and target to tumor cells for its micrometer diamete. Nano liquid fluorocarbon nanoparticles can pass through the endothelial gap and target to tumor cells, but its ultrasound imaging quality is not good, and can not make full use of UTMD for the release of drugs. Our previous study has proved that pulse laser can trigger the phase transition of nanoparticles made by perfluorohexan (PFH) and optical absorbers, rational utilization of the photoacoustic effect can achieve the aim of imaging and treatment to the tumor. Retinoblastoma (RB) is the most common intraocular malignant tumor in infants and young children. It is lack of early diagnosis and effective treatment. Laser can be widely used in the treatment of retinal diseases, because it can pass through clearing medium. So, this project proposed to develop a photoacoustic / ultrasonic molecular probe, which could target to the folate receptor of RB cells, and with perfluoro pentane (PFP) as the core, carrying adriamycin (ADM) and optical absorption of indocyanine green (ICG), lipid inclusions and has the ability of liquid gas phase transition. When used in vitro or in vivo, it could target to RB cells, and with pulse laser irradiation, the molecular probe will undergo a phase transition and produce microbubbles and photoacoustic effect, and release ADM from bubbles, make the chemotherapy combined with photo acoustic therapy efficiently, reduce its systemic toxicity, and make the photoacoustic / ultrasonic dual mode molecular imaging coming true.