多功能银纳米复合物在肿瘤光热-化疗联合治疗中的应用研究

乳腺癌是女性最常见的恶性肿瘤，由于耐药性和复发转移现象日益严重，如何进一步提升治疗效果面临着重大挑战。大量证据表明，肿瘤干细胞在肿瘤的复发、转移和治疗抵抗中起着关键性作用。此外，光热治疗与化疗可产生协同作用，而纳米银也可与化疗药产生协同作用，且三角形纳米银还具有良好的光热转换性能。因此，以三角形纳米银为基础开发同时针对乳腺癌细胞和乳腺癌干细胞的化疗和光热治疗的联合疗法，有望取得良好的治疗效果。

构建双靶点靶向（乳腺癌细胞和乳腺癌干细胞）和双重协同作用（纳米银化疗协同和光热-化疗协同）的载药三角形银纳米复合物。评价该复合物的药动学及生物安全性，研究其靶向特异性、体内生物分布、体内/体外光热疗联合化疗抑制乳腺癌生长和转移的效应及相关分子机制，为乳腺癌的治疗提供新的方法和思路。

纳米医用材料在肿瘤辐射治疗和成像中的应用研究

近年来，脑胶质瘤等恶性肿瘤发病率及死亡率不断上升，且发病年龄呈年轻化趋势。辐射治疗是肿瘤重要治疗手段之一，但大部分肿瘤细胞对射线不敏感，辐射治疗效果亦不佳。如何增强肿瘤细胞的辐射敏感性，有效提高射线对肿瘤细胞的特异性杀伤，一直是临床上亟待解决的热点问题。另一方面，目前临床上相对分离的诊断与治疗模式可能贻误最佳治疗时机，增加患者不必要的痛苦和风险，且在治疗过程中不能同步、动态跟踪治疗效果。为此，应用不断创新的生命科学的前沿技术，寻找切实可用的分子靶标，利用具有诊断与辐射增敏功能一体化的高效诊疗剂，有望解决这些难题。

研究Ag@Au、Ag和Au等纳米材料的靶向设计与构建、生物安全性、肿瘤成像及材料辐射增敏对肿瘤转归的影响，探讨免疫反应及自噬在肿瘤治疗中的作用及其调控，寻找纳米材料辐射增敏抗瘤关键通路信号分子。研究结果有助于肿瘤新型诊疗剂的研发。

东南大学教学一等奖

东南大学优秀共产党员

常州市人民政府奖教金

许国平奖教金

东南大学“三育人”积极分子

Selected Publications

1.Peidang Liu,Huimin Shao, Yan Kong, Dayong Wang. Effect of graphene oxide exposure onintestinal Wnt signaling in nematode Caenorhabditis elegans. J EnvironSCI-CHINA, 2020, 88: 200-208.

2.Jing Zhao, Peidang Liu*, Jun Ma, Dongdong Li,Huiquan Yang, Wenbin Chen, Yaowen Jiang. Enhancement of radiosensitization bysilver nanoparticles functionalized with polyethylene glycol and aptamer As1411for glioma irradiation therapy. Int J Nanomed, 2019, 14: 9483-9496.

3.Peidang Liu, Dan Li, Wenjie Li, Dayong Wang. Mitochondrial unfolded protein response to microgravitystress in nematode Caenorhabditis elegans. Sci Rep, 2019, 9(1): 16474

4.Peidang Liu*,Huiquan Yang, Wenbin Chen, Jing Zhao, Dongdong Li. Silver nanotrianglesand chemotherapy drugs synergistically induce apoptosis in breast cancer cellsvia production of reactive oxygen species. J Nanopart Res, 2019, 21(11):250.

5.Peidang Liu,Huimin Shao, Xuecheng Ding, Ruilong Yang, Qi Rui, Dayong Wang. Dysregulation ofneuronal Gαo signaling by graphene oxide in nematode caenorhabditis elegans.Sci Rep, 2019, 9(1): 6026

6. Feng Chen, Xiao Hong Zhang, Xiao Dan Hu, Pei Dang Liu* and Hai Qian Zhang*. The effects of combined selenium nanoparticles and radiation therapy on breast cancer cells in vitro. Artif Cells Nanomed Biotechnol. 2018, 46(5): 937-948.

7. Feng Chen, Xiao Hong Zhang, Xiao Dan Hu, Pei Dang Liu* and Hai Qian Zhang*. Mechanisms of increased in vitro radio sensitivity by a ceria nanoparticle-neogambogic acid combination. Nanosci and Nanotech Lett. 2018, 10(2): 259-266

8. Ningning Ma, Peidang Liu, Nongyue He, Ning Gu, Fu-Gen Wu, and Zhan Chen. Action of Gold Nanospikes-Based Nanoradiosensitizers: Cellular Internalization, Radiotherapy, and Autophagy. ACS Appl Mater Interfaces, 2017, 9(37): 31526-31542.

9. Peidang Liu*, Haizhen Jin, Zhirui Guo, Jun Ma, Jing Zhao, Dongdong Li, Hao Wu and Ning Gu*. Silver nanoparticles outperform gold nanoparticles in radiosensitizing U251 cells in vitro and in an intracranial mouse model of glioma. Int J Nanomed. 2016; 11: 5003-5014.

10. Feng Chen, Xiaohong Zhang, Xiaodan Hu, Weizhang, Rong Zeng, Peidang Liu* and Haiqian Zhang*. Synthesis and characteristics of nanorods of gadolinium hydroxide and gadolinium oxide. J Alloy Compd. 2016, 664: 311-316.

11. Hao Wu, Jun Lin, Peidang Liu, Zhihai Huang, Peng Zhao, Haizhen Jin, Jun Ma, Longping Wen, Ning Gu. Reactive oxygen species acts as executor in radiation enhancement and autophagy inducing by AgNPs. Biomaterials. 2016; 101: 1-9.

12. Zhichao Lou, Zhiwei Zhou, Wei Zhang, Xiaohong Zhang, Xiaodan Hu, Peidang Liu*, Haiqian Zhang*. Magnetized bentonite by Fe3O4 nanoparticles treated as adsorbent formethylene blue removal from aqueous solution: Synthesis, characterization, mechanism, kinetics and regeneration. J Taiwan Inst Chem E. 2015, 49:199-205.

13. Feng Chen, Xiaohong Zhang, Xiaodan Hu, Wei Zhang, Zhichao Lou, Lihua Xie, Peidang Liu* and Haiqian Zhang*. Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells. Int J Nanomed. 2015, 10:4957-4969.

14. Xiangyu Su, Peidang Liu, Hao Wu, Ning Gu. Enhancement of radiosensitization by metal-based nanoparticles in cancer radiation therapy. Cancer Biol Med, 2014, 11 (2): 86-91.

15. Xiaodong Zhang, Fugen Wu, Peidang Liu, Ning Gu, Zhan Chen. Enhanced fluorescence of gold nanoclusters composed of HAuCl4 and histidine by glutathione: glutathione detection and selective cancer cell imaging. Small, 2014, 10 (24): 5170-5177.

16. Peidang Liu, Zhihai Huang, Zhongwen Chen, Ruizhi Xu, Hao Wu, Fengchao Zang, Cailian Wang, and Ning Gu. Silver nanoparticles: a novel radiation sensitizer for glioma? Nanoscale, 2013, 5 (23): 11829-11836.

17. Peidang Liu, Zhihai Huang, Ning Gu. Exposure to silver nanoparticles does not affect cognitive outcome or hippocampal neurogenesis in adult mice. Ecotox Environ Safe, 2013, 87: 124-130.

18.刘培党, 史婷婷, 朱建宝, 曾水林, 顾宁. 纳米银联合放疗对大鼠胶质瘤内iNOS表达和NO水平的影响. 神经解剖学杂志, 2013, 29 (3): 275-279.

19. Peidang Liu, Kewen He, Yinxia Li, Qiuli Wu, Peng Yang, and Dayong Wang. Exposure to mercury causes formation of male-specific structural deficits by inducing oxidative damage in nematodes. Ecotox Environ Safe, 2012, 79: 90-100.

20. Qiuli Wu#, Peidang Liu#, Yinxia Li, Min Du, Xiaojuan Xing, and Dayong Wang. Inhibition of ROS elevation and damage on mitochondrial function prevents lead-induced neurotoxic effects on structures and functions of AFD neurons in Caenorhabditis elegans. J Environ SCI-CHINA, 2012, 24 (4): 733-742.

21. Peidang Liu, Ling Chen, Xiuying Bai, Andrew Karaplis, Dengshun Miao, and Ning Gu. Impairment of spatial learning and memory in transgenic mice overexpressing human fibroblast growth factor-23. Brain Res, 2011, 1412: 9-17.