恶性肿瘤严重危害人类健康，化疗是其主要治疗手段之一。但常规化疗药物缺乏靶向性，在杀灭恶性肿瘤的同时也不可避免的损伤正常细胞，从而出现不良反应，加之部分化疗药物水溶性差，严重限制了其临床应用。透明质酸纳米药物具有多种优点：1)生物相容性良好、可降解，改善药物水溶性和稳定性，延长在血液中半衰期；2)通过主动和被动双靶向作用，使药物在肿瘤细胞中蓄集，实现靶向给药，增加肿瘤的给药效率，提高疗效；3)封装在透明质酸纳米载体内的药物被肿瘤部位活化的透明质酸酶降解后释放，减少毒副作用。本研究拟合成一种具有自主知识产权的双靶向透明质酸纳米化疗药物，应用在五种肿瘤动物模型上，采用18F-FDG和18F-FRGD2小动物PET/CT分子显像，观察不同时间点肿瘤部位葡萄糖代谢和新生血管变化。本项目有望为透明质酸纳米化疗药物的设计、合成提供新思路，实现PET/CT多角度早期监测其疗效的目标，为其临床转化提供依据。

Malignant tumors cause serious damages to the human's health. Chemotherapy is one of the main strategies for the clinical treatment of cancer, however, the lack of targeting capacity, severe side effects and poor water solubility largely limited chemotherapy drugs applications in clinic. To this end, hyaluronic acid nanodrugs were preparated due to several advantages: 1) low immunogenicity, good biocompatibility, biodegradable, improvided water solubility and stability and prolonged the half-life in blood; 2) through the active and passive targeting effect, improving the drug accumulations in the tumor cells, increasing the tumor's drug delivery efficiency and improving the effect of treatment; 3) encapsulated in hyaluronic acid based polymer nanoparticles (HANPs) anti-cancer nanodrugs are degrated and released by activated hyaluronidase in tumor sites, which reduces drug side effects caused by systemic diffusion. In this study, we will prepare the dual targeted HANPs' nanodrugs with independent intellectual property rights and test on five kinds of animal models. We will use 18F-FRGD2 and 18F-FDG micro PET/CT to accurately and noninvasively monitor the early therapy response during the therapy and evaluate the biochemical changes and metabolic states of tumor tissues early. This project is promising to provide new ideas for the design and synthesis of HANPs' nanodrugs and confirm the feasibility of monitoring the curative effect, providing the basis for its clinical translation.