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

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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.

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

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Publication details

The article was received on 31 Aug 2019, accepted on 15 Oct 2019 and first published on 15 Oct 2019


Article type: Edge Article
DOI: 10.1039/C9SC04389F
Chem. Sci., 2019, Advance Article
  • Open access: Creative Commons BY license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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

    Y. Xing, Z. Cai, M. Xu, W. Ju, X. Luo, Y. Hu, X. Liu, T. Kang, P. Wu, C. Cai and J. Zhu, Chem. Sci., 2019, Advance Article , DOI: 10.1039/C9SC04389F

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