凌代舜课题组疾病微环境调控纳米酶研究进展

疾病微环境具有许多异于正常组织的特征，在疾病的发生和发展中起着重要作用。例如，肿瘤微环境pH呈弱酸性，活性氧（ROS）含量较高，且局部缺氧；组织损伤微环境中ROS含量异常升高，且往往伴随着炎症的发生。因此，疾病微环境中这些区别于正常组织的特征可以为开发新型诊疗药物提供生理病理基础。纳米酶是一类具有模拟生物酶活性的纳米材料，在肿瘤治疗、再生医学等相关领域受到了越来越多的关注。例如，具有超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性的纳米酶可清除生物体内过量的ROS，在神经退行性疾病、组织损伤、炎症等疾病中得到了应用；具有氧化酶（OXD）和过氧化物酶（POD）活性的纳米酶可促进ROS的生成，从而实现肿瘤抑制、抗菌等治疗效果1,2,3。近年来，浙江大学凌代舜课题组针对疾病微环境特征，在纳米酶可控合成和组装、进而实现对微环境的调控以及对疾病的高效诊疗方面取得了一系列进展。

01

肿瘤微环境调控

图1. 生物降解介导的酶活性可控氧化钼纳米酶用于肿瘤特异性级联催化治疗

02

肝损伤微环境调控

图2. 具有双重调节作用的氧化铈纳米酶用于治疗APAP诱导的肝损伤

03

皮肤创伤微环境调控

图3. 利用氧化铈纳米酶水凝胶促进糖尿病创面微环境中的血管生成

04

神经退行性疾病微环境调控

图4. 基于氧化铈纳米酶的tau蛋白靶向多功能纳米组装体用于AD诊断和治疗

参 考 文 献

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3. Jiang, D., Ni, D., Rosenkrans, Z. T., Huang, P., Yan, X., Cai, W., Nanozyme: new horizons for responsive biomedical applications. Chem. Soc. Rev. 2019, 48, 3683-3740.

4. Hu, X., Li, F., Xia, F., Guo, X., Wang, N., Liang, L., Yang, B., Fan, K., Yan, X., Ling, D., Biodegradation-mediated enzymatic activity-tunable molybdenum oxide nanourchins for tumor-specific cascade catalytic therapy. J. Am. Chem. Soc., 2020, 142, 1636-1644.

5. Li, F., Qiu, Y., Xia, F., Sun, H., Liao, H., Xie A., Lee, J., Lin, P., Wei, M., Shao, Y., Yang, B., Weng, Q., Ling, D., Dual detoxification and inflammatory regulation by ceria nanozymes for drug-induced liver injury therapy. Nano Today, 2020, 35,100925.

6. Wu, H., Li, F., Wang, S., Lu, J., Li, J., Du, Y., Sun, X., Chen, X., Gao, J., Ling, D., Ceria nanocrystals decorated mesoporous silica nanoparticle based ROS-scavenging tissue adhesive for highly efficient regenerative wound healing. Biomaterials, 151, 66-77.

7. Wu, H., Li, F., Shao, W., Gao, J., Ling, D., Promoting angiogenesis in oxidative diabetic wound microenvironment using a nanozyme-reinforced self-protecting hydrogel. ACS Cent. Sci., 2019, 5, 477-485.

8. Chen, Q., Du, Y., Zhang, K., Liang, Z., Li, J., Yu, H., Ren, R., Feng, J., Jin, Z., Li, F., Sun, J., Zhou, M., He, Q., Sun, X., Zhang, H., Tian, M., Ling, D., Tau-targeted multifunctional nanocomposite for combinational therapy of alzheimer’s disease. ACS nano, 2018, 12, 1321-1338.

撰稿：夏凡

审改：武江洁星、徐风梧