肝癌是严重影响人类健康的恶性肿瘤之一，目前的药物治疗因全身毒副作用大和缺乏靶向性而疗效不佳。本研究针对肝癌药物治疗靶向性差和疗效响应监测缺失等临床问题，以纳米多壳介孔中空二氧化锆球为核心材料，利用其多壳间的空间装载纳米影像探针与特异性细胞毒性化疗药物，表面偶联靶向分子与智能开关，构建新型药物控释系统。利用肿瘤供血动脉介入途径给药、无机纳米材料的肿瘤EPR效应、材料表面主动靶向分子修饰、材料热触发智能开关控制实现肝癌程序性靶向治疗，将特异性细胞毒性药物直接输送至敏感细胞器，达到最大限度的杀伤肿瘤和降低全身毒副作用的目的。拟通过能谱CT、MRI和基于碘131-金丝桃素坏死靶向SPECT的多模态成像方法进行肿瘤局部药物浓度监测、治疗早期和晚期的疗效评价，进行全面的治疗响应监测。以期通过本研究开辟肝癌靶向化疗的新途径，建立一套高效的肝癌靶向治疗策略和疗效响应监测方法，提高肝癌患者药物治疗的疗效。

Hepatocellular carcinoma (HCC) is one of the most malignant tumors which do harm to human health seriously. At present, the drug therapy is not satisfactory because of its systemic toxicity and lack of targets. In this study, we construct the new targeting drug control release system for HCC with multi-shell nano hollow mesoporous ZrO2 ball, loading specific cytotoxic drugs in the space between the shells. To reach the maximum tumor-killing effect and reducing the systemic side effects, the programmed targeting therapy of HCC will be achieved by interventional approach directly to tumor feeding artery, enhanced permeability and retention (EPR) effect of inorganic nano material in tumor, modification with active targeting molecules to deliver the specific drugs to the sensitive organelles, and control by intelligent thermal trigger switch. It is proposed by using the multimodal imaging methods for evaluation of the efficacy of local tumor drug concentration and treatment efficacy. Tumor response will be monitored by spectral CT, MRI and SPECT-CT based on necrosis-targeted 131I-hypericin. Through this study it is planned to find new ways of targeting chemotherapy, to establish an efficient method for monitoring targeting treatment strategies, to improve the efficacy of drug therapy, and to prolong the survival of patients with HCC.