Revealing chemical processes and kinetics of drug action within single living cells via plasmonic Raman probes

Sci Rep. 2017 May 23;7(1):2296. doi: 10.1038/s41598-017-02510-9.

Abstract

Better understanding the drug action within cells may extend our knowledge on drug action mechanisms and promote new drugs discovery. Herein, we studied the processes of drug induced chemical changes on proteins and nucleic acids in human breast adenocarcinoma (MCF-7) cells via time-resolved plasmonic-enhanced Raman spectroscopy (PERS) in combination with principal component analysis (PCA). Using three popular chemotherapy drugs (fluorouracil, cisplatin and camptothecin) as models, chemical changes during drug action process were clearly discriminated. Reaction kinetics related to protein denaturation, conformational modification, DNA damage and their associated biomolecular events were calculated. Through rate constants and reaction delay times, the different action modes of these drugs could be distinguished. These results may provide vital insights into understanding the chemical reactions associated with drug-cell interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Camptothecin / pharmacology
  • Chemical Phenomena
  • Cisplatin / pharmacology
  • Female
  • Fluorouracil / pharmacology
  • Gold / chemistry
  • Humans
  • Kinetics
  • MCF-7 Cells
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / ultrastructure
  • Principal Component Analysis
  • Protein Denaturation / drug effects*
  • Single-Cell Analysis / methods*
  • Spectrum Analysis, Raman / methods*

Substances

  • Antineoplastic Agents
  • Gold
  • Cisplatin
  • Fluorouracil
  • Camptothecin