基于携带双适体载药纳米囊泡的前列腺癌诊疗一体化基础研究

The early prostate cancer was difficult to be detected by traditional medical imaging examination, and clinical treatment of prostate cancers faced the dilemma that androgen dependent prostate cancer (ADPC) was apt to transform into androgen independent prostate cancer(AIPC), even hormone refractory prostate cancer (HRPC), leading to treatment failure, even death of patients. This study were to construct a small and highly efficient ultrasound nanotheranostic agent used by PEG, PLGA, PFOB, and doxorubicin, which can bind prostate cancer specifically by means of the aptamer A10-3.2 and DUP-1. A serial of experiments were designed to explore the ability and mechanism of ultrasound nanotheranostic agent for targeted imaging and chemotherapy of prostate cancer in vitro and in vivo. The ultimate goal is to achieve a novel nanotheranostic agent that has ability for early tumor detection and targeted delivery chemotherapy drug for prostate cancer under molecular imaging guide. The course of targeted imaging and treatment could help us understand the development and prognosis of prostate cancer. The project will provide a new insight for early diagnosis and targeted therapy of prostate cancer.

针对目前传统的影像学检查方法难以发现早期前列腺癌，以及临床治疗过程中面临雄激素依赖性前列腺癌易转化为激素非依赖性前列腺癌，甚至激素难治性前列腺癌，导致患者预后差、死亡率高等问题，本研究尝试利用聚乙二醇（PEG）、聚乳酸-羟基乙酸共聚物（PLGA）、PFOB等材料，构建一种能装载阿霉素的纳米级超声诊疗剂，并通过适体A10-3.2、DUP-1将其与前列腺癌细胞膜上的特异性膜抗原（PSMA）相连接，赋予其靶向显像及靶向治疗功能，通过一系列体内、体外实验，从细胞、组织、活体动物水平验证其靶向显像和治疗能力，并初步探讨载阿霉素的纳米级超声诊疗剂作用机制。本研究旨在获得一种新型双适体载阿霉素纳米级超声诊疗剂，使得其不仅能够实现在分子成像的监控下对肿瘤实行靶向成像及治疗，还能帮助了解前列腺癌发生、发展、转归等进程改变，这将为前列腺癌的早期诊断与靶向治疗开辟新的方法和思路。

针对目前传统的影像学检查方法难以发现早期前列腺癌，以及临床治疗过程中面临雄激素依赖性前列腺癌易转化为激素非依赖性前列腺癌，甚至激素难治性前列腺癌，导致患者预后差、死亡率高等问题，本研究尝试利用聚乙二醇（PEG）、聚乳酸-羟基乙酸共聚物（PLGA）、PFOB等材料，构建一种能装载阿霉素的纳米级超声诊疗剂，并通过适体A10-3.2、DUP-1将其与前列腺癌细胞膜上的特异性膜抗原（PSMA）相连接，赋予其靶向显像及靶向治疗功能，通过一系列体内、体外实验，从细胞、组织、活体动物水平验证其靶向显像和治疗能力，并初步探讨载阿霉素的纳米级超声诊疗剂作用机制。本研究旨在获得一种新型双适体载阿霉素纳米级超声诊疗剂，使得其不仅能够实现在分子成像的监控下对肿瘤实行靶向成像及治疗，还能帮助了解前列腺癌发生、发展、转归等进程改变，这将为前列腺癌的早期诊断与靶向治疗开辟新的方法和思路。