本文构建了一种多生物响应自组装纳米药物输送系统HSSG，它是通过将抗癌药物生育醇(GER)通过二硫键与透明质酸(HA)连接而形成的。HSSG NPs呈现出均匀的球形形态，平均直径约为110nm，具有高稳定性，在肿瘤微环境(pH /谷胱甘肽/透明质酸酶)中实现了控制药物释放 。荧光显微镜和流式细胞术研究表明，HSSG NPs通过CD44受体介导的内吞作用选择性地被人肝癌细胞株HepG2和Huh7摄取。对H22肿瘤携带的小鼠的研究表明，HSSG NPs能够有效地长时间积累在肿瘤部位。体外和体内研究表明，与GER相比，HSSG NPs显著促进了癌细胞的死亡，同时降低了毒性。因此，HSSG NPs在肿瘤治疗中具有巨大的潜力。 版权所有 © 2023 Elsevier Ltd. 发布。

Herein, a multi-bioresponsive self-assembled nano-drug delivery system (HSSG) was constructed by conjugating the anticancer drug Geraniol (GER) to hyaluronic acid (HA) via a disulfide bond. The HSSG NPs displayed a uniform spherical shape with an average diameter of ∼110 nm, maintained high stability, and realized controlled drug release in the tumor microenvironment (pH/glutathione/hyaluronidase). Results of fluorescence microscopy and flow cytometry verified that HSSG NPs were selectively uptaken by human hepatocellular carcinoma cell lines HepG2 and Huh7 via CD44 receptor-mediated internalization. Studies on H22 tumor-bearing mice demonstrate that HSSG NPs could effectively accumulate at the tumor site for a long period. In vitro and in vivo studies show that HSSG NPs significantly promoted the death of cancer cells while reducing the toxicity as compared to GER. Therefore, the HSSG NPs have great potential in the treatment of tumors.Copyright © 2023. Published by Elsevier Ltd.