抵抗细胞死亡是肿瘤的显著特征，也是治疗的重要靶标之一。我们近期研究发现用硫酸化的N-乙酰氨基葡萄糖修饰的纳米粒子能够选择性诱导癌细胞凋亡，无需化疗药物参与并呈现出优良的治疗效果。基于对硫酸乙酰肝素调节肿瘤信号且功能受硫酸基位点影响的理解，我们准确化学合成了具有不同硫酸基位点的糖单元并制备为硫酸化糖纳米粒子，初步实验结果表明材料会影响癌细胞内Bcl-2蛋白家族的表达水平，且这一活性受粒子表面糖单元硫酸基位点和密度调节。本项目将在此基础上进一步调控硫酸化糖纳米粒子的结构，系统比较不同糖单元结构（类别、硫酸化位点、密度）以及纳米粒子材料特征（尺寸、形貌、软硬度）对诱导肿瘤凋亡作用的影响，在肺癌肿瘤模型上验证治疗效果；阐明硫酸化糖纳米粒子结构-活性-安全性之间的关系，揭示通过结构调节糖纳米材料活性的规律。上述研究将为癌症的糖疗法提供新的思路，并为发展一类新型的糖纳米材料提供依据。

Resistance to cell death is a prominent feature of tumors and also one of the critical targets for treatment. We recently found that sulfated N-acetylglucosamine (GlcNAc) modified nanoparticles could selectively induce tumor cell apoptosis without the involvement of chemotherapy drugs, resulting in excellent efficacy. Based on the understanding that heparan sulfate regulates the tumor signaling and is affected by its sulfation pattern, we prepared a series of sulfated glycosylated nanoparticles (SGNPs) with different well-defined sulfated GlcNAc groups. The preliminary data showed that the SGNPs induced tumor apoptosis by affecting the expression level of Bcl-2 family proteins, and this activity was regulated by the sulfation pattern and the density of glycosyl groups on SGNPs. In this project, we intend to systematically compare the influence of the structure of SGNPs on induction tumor apoptosis by adjusting the structure of glycosyl group (type, sulfation pattern, and density) and the characteristics of nanoparticles (size, morphology, and softness-hardness). The efficacy of SGNPs is going to be validated on lung cancer cells and tumor models. Additionally, we aim to demonstrate the relationship between structure-activity-safety of SGNPs and reveal the principle of regulation the activity by varying the structure of SGNPs. The implementation of this project will provide experimental and theoretical bases for the construction and application of glycosylated nanomaterials in specific tumor treatment in the clinic.