Raman observation of a molecular signaling pathway of apoptotic cells induced by photothermal therapy
Yingfang Xing1, Zhewei Cai2, Meijuan Xu3
1Jiangsu 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 ;
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.
Insights
Gold nanostars enable photothermal therapy (PPTT) to induce cancer cell apoptosis. This study reveals the molecular pathway, including cytochrome c release and DNA fragmentation, crucial for advancing PPTT clinical applications.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Plasmonic nanoparticle (NP)-mediated photothermal therapy (PPTT) is a promising cancer treatment.
- Understanding the molecular mechanisms of PPTT-induced apoptosis is vital for clinical advancement.
- The precise molecular signaling pathway of PPTT-induced apoptosis remains under investigation.
Purpose of the Study:
- To elucidate the molecular mechanism of apoptosis induced by PPTT using gold nanostars (Au NSs).
- To monitor real-time cellular and molecular changes during PPTT-induced apoptosis using surface-enhanced Raman spectroscopy (SERS).
- To identify the specific apoptosis signaling pathway activated by Au NS-mediated PPTT.
Main Methods:
- Utilized nuclear-targeting gold nanostars (Au NSs) as both photothermal agents and SERS probes.
- Monitored time-dependent SERS spectra of MCF-7 cells undergoing apoptosis.
- Analyzed SERS correlation maps, metabolomics, agarose gel electrophoresis, and western blot to identify molecular events.
Main Results:
- Revealed a cascade of molecular events during PPTT-induced apoptosis, including cytochrome c release, protein degradation, and DNA fragmentation.
- Demonstrated that PPTT-induced apoptosis follows an intrinsic mitochondria-mediated pathway.
- Identified the BH3-only protein BID as an initiator of this mitochondria-mediated apoptosis pathway.
Conclusions:
- The study clarifies the molecular mechanism of PPTT-induced apoptosis, specifically the intrinsic mitochondria-mediated pathway initiated by BID.
- SERS provides a powerful tool for real-time monitoring of molecular events during apoptosis.
- Findings will aid in optimizing PPTT for improved cancer therapy efficacy and clinical translation.
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