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Updated: Jun 19, 2026
An Integrated Raman Spectroscopy and Mass Spectrometry Platform to Study Single-Cell Drug Uptake, Metabolism, and Effects
Published on: January 9, 2020
Evaluating the global cellular pharmacological effects of photodynamic therapy using label-free surface-enhanced
Qingxia Zhu1, Qing Zhou2, Shiwei Wang3
1School of Pharmacy, Naval Medical University, Shanghai 200433, China; Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, China; College of Clinical Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Photodynamic therapy (PDT) has attracted widespread attention as an emerging cancer treatment, yet real-time monitoring of tumor oxidative stress during therapy remains challenging due to unclear mechanistic insights, delayed efficacy evaluation, and inefficient drug screening. This study employed label-free dynamic surface-enhanced Raman spectroscopy (D-SERS) to evaluate the cellular pharmacological effects of PDT, enabling the mechanism-based classification of agents. Label-free D-SERS was used to monitor real-time spectral changes in human melanoma cells during PDT, characterizing the differences between apoptosis-inducing (type A) and necrosis-inducing (type B) photosensitizers. Type A exhibited concentration-dependent increases in Raman peaks at 652, 742, 828, and 1000 cm-1, a trend absent in Type B. By analyzing DNA, lipid, and amino acid peak ratios, cells treated with these photosensitizers were clearly classified into two mechanistic groups (A and B). Furthermore, D-SERS was applied to study the Type B agent 5-ALA in combination with heme oxygenase-1 (HO-1) modulators, verifying the associated enzyme-regulatory processes. This study presents a proof-of-concept model for the spectral mechanism-based screening of photosensitizers and enzyme modulators, thus aiding the optimization of PDT efficacy and targeted drug development.
Insights
Dynamic surface-enhanced Raman spectroscopy (D-SERS) offers real-time monitoring of photodynamic therapy (PDT) effects. This label-free method distinguishes cancer drug mechanisms, aiding in efficient photosensitizer and enzyme modulator screening for improved PDT efficacy.
Area of Science:
- Biomedical Spectroscopy
- Cancer Research
- Photodynamic Therapy
Background:
- Photodynamic therapy (PDT) is a promising cancer treatment, but real-time monitoring of tumor oxidative stress and drug mechanisms is challenging.
- Current methods face limitations in mechanistic insight, delayed efficacy evaluation, and inefficient drug screening.
Purpose of the Study:
- To develop and validate a label-free dynamic surface-enhanced Raman spectroscopy (D-SERS) method for real-time evaluation of PDT's cellular pharmacological effects.
- To enable mechanism-based classification of photosensitizers and facilitate screening of therapeutic agents.
Main Methods:
- Utilized label-free D-SERS to monitor real-time spectral changes in human melanoma cells during PDT.
- Characterized spectral differences between apoptosis-inducing (Type A) and necrosis-inducing (Type B) photosensitizers.
- Analyzed DNA, lipid, and amino acid peak ratios for mechanistic classification.
Main Results:
- D-SERS successfully differentiated Type A and Type B photosensitizers based on distinct Raman peak changes.
- Cells were clearly classified into two mechanistic groups (A and B) by analyzing key biomolecular peak ratios.
- Demonstrated D-SERS application in studying 5-ALA combined with heme oxygenase-1 (HO-1) modulators, verifying enzyme-regulatory processes.
Conclusions:
- Presents a proof-of-concept for spectral mechanism-based screening of photosensitizers and enzyme modulators using D-SERS.
- This approach can aid in optimizing PDT efficacy and accelerating targeted drug development.
- D-SERS provides a valuable tool for real-time mechanistic insights into PDT and related therapeutics.
