In this work, a promising treatment strategy for triggering robust antitumor immune responses in transarterial chemoembolization of hepatocellular carcinoma (HCC) is presented. The zeolitic imidazolate framework nanoparticles loaded with hypoxia-activated prodrug tirapazamine and immune adjuvant resiquimod facilitated in situ generation of nanovaccine via a facile approach. The nanovaccine can strengthen the ability of killing the liver cancer cells under hypoxic environment, while was capable of improving immunogenic tumor microenvironment and triggering strong antitumor immune responses by increasing the primary and distant intratumoral infiltration of immune cells such as cytotoxic T cells. Moreover, a porous microcarrier, approved by FDA as pharmaceutical excipient, was designed to achieve safe and effective delivery of the nanovaccine via transarterial therapy in rabbit orthotopic VX2 liver cancer model. The microcarrier exhibited the characteristics of excellent drug loading and occlusion of peripheral artery. The collaborative delivery of the microcarrier and nanovaccine demonstrated an exciting inhibitory effect on solid tumors and tumor metastases, which provided a great potential as novel combination therapy for HCC interventional therapy.

在这项工作中，提出了一种有前途的治疗策略，可在肝细胞癌（HCC）的经动脉化疗栓塞术中触发强大的抗肿瘤免疫反应。载有缺氧激活的前药替拉扎明和免疫佐剂瑞喹莫特的沸石咪唑酯框架纳米颗粒通过简便的方法促进了纳米疫苗的原位生成。该纳米疫苗可以增强缺氧环境下杀伤肝癌细胞的能力，同时能够通过增加细胞毒性T细胞等免疫细胞的原发性和远处瘤内浸润来改善免疫原性肿瘤微环境，引发强烈的抗肿瘤免疫反应。此外，一种经 FDA 批准作为药用辅料的多孔微载体被设计用于通过动脉治疗在兔原位 VX2 肝癌模型中实现安全有效的纳米疫苗递送。该微载体表现出良好的载药性和外周动脉闭塞特性。微载体和纳米疫苗的协同递送对实体瘤和肿瘤转移表现出令人兴奋的抑制作用，这为肝癌介入治疗的新型联合疗法提供了巨大的潜力。