基于锰螯合介孔聚多巴胺的T1-T2双模MRI可视化肝癌纳米诊疗体系

早期诊断和高效药物治疗是提高肝癌患者生存率的关键，磁共振成像（MRI）是临床肝癌诊断的常用工具，T1造影剂尽管在识别肿瘤微浸润方面具有优势，但其灵敏度显著低于T2造影剂，难以检出小于1cm的早期肝癌，缺乏兼具T1及T2的高性能造影剂是制约MRI进行肝癌早期诊断的重大难题；此外，肝癌现有药物治疗手段（包括常规化疗及分子靶向治疗药物）均存在疗效欠佳及易产生耐药等不足，急需发展新型高效的药物治疗手段。针对上述难题，拟基于肿瘤微环境响应的锰螯合介孔聚多巴胺纳米材料，制备新型肝癌诊疗探针，不仅具有高灵敏T1/T2双模MRI造影功能，而且通过包载双氢青蒿素可实现肝癌的影像可视化声动力治疗；外源超声辐照与内源微环境刺激响应相结合的策略显著增强对肝癌的治疗效果。本项目针对肝癌临床诊疗的瓶颈性难题，不仅可望获得新型高灵敏MRI探针，而且有望改善肝癌的药物治疗效果，从而为高效肝癌诊疗提供新思路及技术基础。

Early diagnosis and effective treatment are the key to improving the survival rate of hepatocellular carcinoma. Magnetic resonance imaging (MRI) is commonly used for the clinical diagnosis of hepatoma. Although T1 contrast agent is used for its advantage in identifying tumor infiltration, its sensitivity is significantly lower than that of T2 contrast agent. Therefore, it’s difficult to detect early hepatoma smaller than one centimeter. The lack of high performance contrast agents with combined advantages of both T1 and T2 is a major problem limiting the early diagnosis of hepatoma by MRI. Moreover, the therapeutic effects of existing drug treatments for hepatoma (including conventional chemotherapy and targeted therapy are far from satisfactory, which may also cause drug resistance. Therefore, it’s urgent to develop new and efficient drug treatment. With respect to these challenges, a novel theranostic probe based on manganese chelated mesoporous polydopamine nanomaterials with tumor microenvironment response is proposed. It not only has the high sensitivity of T1/T2 dual-mode MRI, but also can achieve the visualized sonodynamic treatment of hepatoma by encapsulating dihydroartemisinin (DHA). The combination of external ultrasound irradiation and internal microenvironment stimulation is expected to significantly enhance its therapeutic effect of hepatoma. Aiming at solving the bottlenecks in the clinical theranostic of hepatoma, this study could not only provide a novel and efficient highly sensitive MRI probe, but also improve the effect of drug treatment. This study provides a novel approach and technical implementations to the efficient diagnosis and treatment of hepatoma.