近日,我校中医药创新研究院张振教授带领的生物传感与靶向免疫研究团队与上海大学、重庆大学等合作报道了恶性肿瘤早期分子分型、原位诱导癌细胞焦亡、激活免疫系统等新方法,分别以通讯或第一作者在ACS Appl. Mater. Interfaces杂志(影响因子: 10.383,中科院一区Top)上发表了题为Ultrasensitive dual-signal detection of telomerase and miR-21 based on boolean logic operations的论文;在Nanoscale杂志(影响因子: 8.307,中科院一区Top)上发表了题为Combination of DNA demethylation and chemotherapy to trigger cell pyroptosis for inhalation treatment of lung cancer的论文;在Frontiers in pharmacology杂志(影响因子:5.81,中科院二区)上发表了题为 PD-1/PD-L1 checkpoint inhibitors in tumor immunotherapy和Immune effect of active components of traditional Chinese medicine on triple negative breast cancer的文章;在杂志Sensors and Actuators B-Chemical,(影响因子: 9.221,中科院一区Top)上发表了题为Hollow and porous Fe3C-NC nanoballoons nanozymes for cancer cell H2O2 detection和A sensitive amperometric immunosensor for the detection of carcinoembryonic antigen using ZnMn2O4@reduced graphene oxidecomposites as signal amplifier的论文。
创新性地提出一种肺癌原位联合治疗技术,通过肺传递CO-MPs来触发癌细胞焦亡和免疫反应。CO-MPs可以逆转GSDME沉默,提高肿瘤细胞中裂解caspase3的表达。被裂解的caspase3蛋白裂解GSDEM蛋白获得GSDME-N蛋白,导致细胞质膜破裂,细胞内容物的释放和免疫系统的激活。CO-MPs可抑制肺肿瘤,抑制肺转移结节,诱导免疫记忆,提供抑制肿瘤的记忆保护效应。

图1. DNA去甲基化与化疗联合触发细胞焦亡、免疫激活抑制肺癌
设计并制备二酮吡咯基共轭聚合物和F127组合的水溶性纳米药物,其具有优异的光学性能、生物相容性和光稳定性,有利于实现高性能PDT/PTT联合治疗。通过体外和体内实验证实纳米胶囊具有明显的抗肿瘤效应。这项工作为合理设计近红外吸收有机聚合物纳米药物用于恶性肿瘤联合治疗提供新方法。

图2.激光808nm触发PDT/PTT联合治疗恶性肿瘤疾病
针对恶性肿瘤早期诊断遇到的瓶颈问题,基于激光共聚焦荧光、拉曼和原子力成像联合技术,采用端粒酶和miR-21的多信号识别和DNA信号放大技术实现了肿瘤疾病早期的分子分型,这项研究将为恶性肿瘤早期识别和分型提供新方法。

图3.基于端粒酶和miR-21多信号识别放大技术的恶性肿瘤早期分子分型
相关研究成果:
1)Jinhua Liu, Zichao Chen, Yaqun Li, Wenjie Zhao, Jibiao Wu*, Zhen Zhang*, Frontiers in pharmacology,2021, 12, 731798.
2)Jiaju Shi, Meiqi Shen, Wenjie Zhao, Jinhua Liu, Zongjin Qu, Mengting Zhu, Zichao Chen*, Pengfei Shi*, Zhen Zhang*, Shusheng Zhang, ACS Appl. Mater. Interfaces,2021, 13, 43, 51393-51402.
3)Tingting Liu, Shuang Chen, Yan Zhang, Dongxian He, Qian Shao, Zhen Zhang*, ect., Nanoscale, 2021, DOI: 10.1039/D1NR05001J.
4)Wenjie Zhao, Jinhua Liu, Yaqun Li, Zichao Chen, Dongmei Qi*, Zhen Zhang*, Frontiers in pharmacology, 2021, DOI: 10.3389/fphar.2021.731741.
5)Xinxia Fan, Dongmei Deng, Zichao Chen*, ect., Sensors and Actuators B-Chemical, 2021, 339, 129852.
6)Xiaohong Yang, Ruixue Zhang, Jian Guo, Zichao Chen*, ect., Sensors and Actuators B-Chemical, 2021, 347, 130597.
7)Jiawei Liu, Xingpeng Xu, Jing Wang, Ruoyu Sang, Zhen Zhang*, etc., Dyes and Pigments,2021, 196, 109762.