“大黄-栀子”为中医“清热利湿”经典药对，常用于治疗“湿热蕴肠”型溃疡性结肠炎（UC）。前期研究发现该药对有效组分大黄酸-栀子苷可能通过免疫抑制和肠道菌群调控，显著改善小鼠UC症状。但如何实现该组分均衡高效靶部位共递送，为其治疗UC瓶颈。基于申请人博士期间人血清白蛋白（HSA）口服靶向纳米研究，提出假说：采用免疫细胞主动靶向的HSA纳米对大黄酸-栀子苷进行共载，实现免疫靶向和多靶点协同抗UC。.本项目根据HSA高生物相容性和载药性能，进行“大黄酸物理包载-栀子苷化学交联”创新性载药设计，以实现药物多层次包载和载体稳定性增强双重优势；基于UC病灶特征，将OX40单抗修饰于纳米表面以主动识别T细胞；最终构建大黄酸-栀子苷“免疫靶向-逐级释药-多靶响应”共载口服纳米体系，并从mTOR通路免疫抑制和SCFAs分泌菌群调控角度，阐明大黄酸-栀子苷配伍治疗UC机制，为组分中药共传递抗UC提供新思路。

"Rhei Radix et Rhizoma and Gardeniae Fructus" is a classic Chinese herb pair, with the function of clearing heat and promoting dampness. It is often used in treating "dampness-heat accumulated intestine" type of ulcerative colitis (UC). Applicant's previous studies have found that Rhein and Geniposide, two active compounds from Rhei Radix et Rhizoma and Gardeniae Fructus, can significantly relieve the UC symptoms in UC mice model, which might be the effects of immune suppression and intestinal flora regulation of Rhein and Geniposide respectively. However, how to co-deliver these two components to colon directly and efficiently is a big challenge in UC treatment. Based on the previous study about oral human serum albumin (HSA) targeted nanoparticles which was completed by applicant during the PhD study period, a hypothesis is proposed that Rhein and Geniposide layer-encapsulated by HSA nanoparticles with immune cells-targeted function, will show the synergistic effects of components on UC treatment via targeting immune cells and inducing multi-targets response...Based on the characteristics of high biocompatibility and drug loading capacity for HSA, we will design a novel drug co-loading system by physically internal loading of Rhein and chemically crosslinking of Geniposide, which has two obvious advantages of layer-encapsulating drugs and enhancement of carrier stability. Based on pathogenesis of UC, OX40 monoclonal antibody will be further modified on the surface of nanoparticles so as to recognize T lymphocytes around UC lesions. Ultimately, a co-loading components oral delivery system with the function of immune cells-targeted, gradual release and multiple targets response will be constructed. In addition, we will also clarify the mechanism of combination of Rhein and Geniposide in treating UC via immunosuppression of mTOR pathway and regulation of intestinal SCFAs-producing flora though this colon-targeted co-delivery design, which will provide valuable reference to co-delivery herb components research.