Raman observation of a molecular signaling pathway of apoptotic cells induced by photothermal therapy

Yingfang Xing; Zhewei Cai; Meijuan Xu; Wenzheng Ju; Xiaojun Luo; Yaojuan Hu; Xiaoyan Liu; Tuli Kang; Ping Wu; Chenxin Cai; Jun-Jie Zhu

doi:10.1039/c9sc04389f

Raman observation of a molecular signaling pathway of apoptotic cells induced by photothermal therapy

Chem Sci. 2019 Oct 15;10(47):10900-10910. doi: 10.1039/c9sc04389f. eCollection 2019 Dec 21.

Authors

Yingfang Xing¹, Zhewei Cai², Meijuan Xu³, Wenzheng Ju³, Xiaojun Luo¹, Yaojuan Hu¹, Xiaoyan Liu¹, Tuli Kang¹, Ping Wu¹, Chenxin Cai¹, Jun-Jie Zhu⁴

Affiliations

¹ Jiangsu Key Laboratory of New Power Batteries , Jiangsu Collaborative Innovation Center of Biomedical Functional Materials , National and Local Joint Engineering Research Center of Biomedical Functional Materials , College of Chemistry and Materials Science , Nanjing Normal University , Nanjing 210097 , P. R. China . Email: wuping@njnu.edu.cn ; Email: cxcai@njnu.edu.cn.
² Department of Chemical and Biomolecular Engineering , Clarkson University , Potsdam , NY 13699 , USA.
³ Key Laboratory of Department of Clinical Pharmacology , Affiliated Hospital of Nanjing University of Chinese Medicine , China.
⁴ State Key Laboratory of Analytical for Life Science , School of Chemistry & Chemical Engineering , Nanjing University , Nanjing 210093 , P. R. China . Email: jjzhu@nju.edu.cn.

Abstract

Plasmonic nanoparticle (NP)-mediated photothermal therapy (PPTT) has been explored as a minimally invasive approach to cancer therapy and has progressed from concept to the early stage of clinical trials. Better understanding of the cellular and molecular response to PPTT is crucial for improvement of therapy efficacy and advancement of clinical application. However, the molecular mechanism underlying PPTT-induced apoptosis is still unclear and under dispute. In this work, we used nuclear-targeting Au nanostars (Au NSs) as both a photothermal agent to specifically induce apoptosis in cancer cells and as a surface enhanced Raman spectroscopy (SERS) probe to monitor the time-dependent SERS spectra of MCF-7 cells which are undergoing apoptosis. Through SERS spectra and their synchronous and asynchronous SERS correlation maps, the occurrence and dynamics of a cascade of molecular events have been investigated, and a molecular signaling pathway of PPTT-induced apoptosis, including release of cytochrome c, protein degradation, and DNA fragmentation, was revealed, which was also demonstrated by metabolomics, agarose gel electrophoresis, and western blot analysis, respectively. These results indicated that PPTT-induced apoptosis undergoes an intrinsic mitochondria-mediated apoptosis pathway. Combined with western blot results, this intrinsic mitochondria-mediated apoptosis pathway was further demonstrated to be initiated by a BH3-only protein, BID. This work is beneficial for not only improving the fundamental understanding of the molecular mechanism of apoptosis induced by PPTT but also for guiding the modulation of PPTT to drive forward its clinical application.