Investigation of squalene-doxorubicin distribution and interactions within single cancer cell using Raman microspectroscopy

Nanomedicine. 2021 Jul:35:102404. doi: 10.1016/j.nano.2021.102404. Epub 2021 Apr 29.

Abstract

Intracellular distribution of doxorubicin (DOX) and its squalenoylated (SQ-DOX) nanoparticles (NPs) form in murine lung carcinoma M109 and human breast carcinoma MDA-MB-231 cells was investigated by Raman microspectroscopy. Pharmacological data showed that DOX induced higher cytotoxic effect than SQ-DOX NPs. Raman data were obtained using single-point measurements and imaging on the whole cell areas. These data showed that after DOX treatment at 1 μM, the spectral features of DOX were not detected in the M109 cell cytoplasm and nucleus. However, the intracellular distribution of SQ-DOX NPs was higher than DOX in the same conditions. In addition, SQ-DOX NPs were localized into both cell cytoplasm and nucleus. After 5 μM treatment, Raman bands of DOX at 1211 and 1241 cm-1 were detected in the nucleus. Moreover, the intensity ratio of these bands decreased, indicating DOX intercalation into DNA. However, after treatment with SQ-DOX NPs, the intensity of these Raman bands increased. Interestingly, with SQ-DOX NPs, the intensity of 1210/1241 cm-1 ratio was higher suggesting a lower fraction of intercalated DOX in DNA and higher amount of non-hydrolyzed SQ-DOX. Raman imaging data confirm this subcellular localization of these drugs in both M109 and MDA-MB-231 cells. These finding brings new insights to the cellular characterization of anticancer drugs at the molecular level, particularly in the field of nanomedicine.

Keywords: Cancer cells; Nanoparticles; Raman microspectroscopy; Squalenoylated doxorubicin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacokinetics
  • Doxorubicin* / pharmacology
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Mice
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Single-Cell Analysis*
  • Spectrum Analysis, Raman
  • Squalene* / chemistry
  • Squalene* / pharmacokinetics
  • Squalene* / pharmacology

Substances

  • Squalene
  • Doxorubicin