可降解Re-siRNA纳米团簇用于CT引导下胰腺癌介入治疗的研究

Pancreatic cancer is a digestive system tumor with high degree of malignancy and poor prognosis, and its hypovascular and hypoxic characteristics decrease the sensitivity of chemotherapy and radiotherapy, hence it is urgent to develop novel treatments for pancreatic cancer. This project intends to fabricate rhenium (Re) nanoclusters with strong near-infrared absorption, which are covalently linked to the siRNA targeting KRAS gene by Re-S bond to construct biodegradable Re-siRNA nanoclusters with multiple functions including hydrogen peroxide-responsive drug release, CT imaging, photothermal therapy, and gene therapy, and the application in interventional treatment of pancreatic cancer and synergistic therapeutic mechanism are studied. The system not only realizes the combination of imaging and multimodal therapy, overcoming the limitation of monotherapy, but also conquers the problems of nondegradation, single function and large size for most siRNA inorganic nanocarriers. In addition, CT-guided visual injection and precise drug delivery can be achieved with the aid of CT enhancement effect of Re element. The project proposes that highly biocompatible Re nanoclusters are potential biodegradable and multifunctional siRNA nanocarriers, provides new ideas for the design of anti-pancreatic cancer siRNA drugs and may promote the development of interventional treatment of pancreatic cancer.

胰腺癌是一种高度恶性且预后不佳的消化系统肿瘤，乏血和乏氧的生物学特征降低了其对化疗和放疗的敏感性，因此亟待发展新型胰腺癌治疗方法。本项目拟制备具有强近红外吸收的金属铼（Re）纳米团簇，通过Re-S键共价连接上靶向KRAS基因的siRNA，构筑集过氧化氢响应的siRNA释放、CT诊断、光热治疗和基因治疗等多个功能于一体的可降解Re-siRNA纳米团簇，研究其在胰腺癌介入治疗中的应用以及协同治疗机制。既实现影像诊断和多模式联合治疗的有机结合，克服单一疗法的局限性，又改善大多数siRNA无机纳米载体面临的不可降解、功能单一和尺寸较大等问题。此外，借助Re元素的CT增强效果，可实现CT引导下的可视化注射和精准给药。该项目提出高生物相容性Re纳米团簇是一种潜在的可降解多功能siRNA纳米载体，为胰腺癌siRNA药物的设计提供新思路，有望促进胰腺癌介入治疗的发展。