化疗栓塞治疗是临床中晚期肝癌的一线疗法，但接受治疗患者的复发率仍较高，已有研究发现酸性肿瘤微环境与其预后高度相关。我们前期体外实验证实通过改变肿瘤微环境的酸碱度能够提高化疗药的抗肿瘤疗效，但化疗药和碳酸氢钠共载栓塞微球仍未见报道，其抗肿瘤疗效尚不清楚。前期工作中，我们通过S/O/O乳化-溶剂挥发法成功制备阿霉素/碳酸氢钠共载微球（DOX/NaHCO3-MS），细胞实验初步证实其具有较好的抗肝癌疗效。本项目拟：（1）明确并优化DOX/NaHCO3-MS制备的处方工艺和理化性质；（2）体外细胞实验确定DOX/NaHCO3-MS对肝癌细胞增殖、凋亡、侵袭迁移能力、细胞周期的影响，以及对趋化因子、血管生成因子和肿瘤干性标志物表达的影响；（3）基于兔VX2原位肝癌模型，在动物层面确证栓塞、化疗以及肿瘤微环境酸碱度调节能够产生协同抗肝癌作用。本研究将为富血供实体瘤的安全高效精准栓塞治疗提供新思路。

Chemoembolization is the first-line treatment for advanced hepatocellular carcinoma, but the recurrence rate of patients is still high. It has been found that the acidic tumor microenvironment is highly correlated with its prognosis. Our previous in vitro experiments have confirmed that the anti-tumor efficacy of chemotherapeutic drugs can be improved by changing the pH of the tumor microenvironment，but the co-loading of chemotherapy drugs and sodium bicarbonate with embolized microspheres has not been reported, and its anti-tumor efficacy is still unclear. In our pre-experiment，we successfully prepared doxorubicin/sodium bicarbonate co-loaded microspheres (DOX/NaHCO3-MS) by S/O/O emulsification and solvent volatilization, and the cell experiments have initially confirmed that it has a good anti-hepatocarcinoma effect. In this study, we aim to: (1) Defining and optimizing the formulation process and physicochemical properties of DOX/NaHCO3-MS; (2) The in-vitro experiments would be performed to determine the effects of DOX/NaHCO3-MS on proliferation, apoptosis, invasion and migration, cell cycle, and expression of chemokines, angiogenic factors and stemness markers of tumor; (3) The synergistic anti-liver cancer effect of embolization, chemotherapy and tumor microenvironment pH regulation would be confirmed at the animal level based on the VX2 orthotopic liver cancer model of rabbit. This study will provide new ideas for the safety, efficient and precision embolization of blood-rich solid tumors.