Effective elimination of liver cancer stem-like cells by CD90 antibody targeted thermosensitive magnetoliposomes

Oncotarget. 2016 Jun 14;7(24):35894-35916. doi: 10.18632/oncotarget.9116.

Abstract

Aim: To investigate the use of thermosensitive magnetoliposomes (TMs) loaded with magnetic iron oxide (Fe3O4) and the anti-cancer stem cell marker CD90 (CD90@TMs) to target and kill CD90+ liver cancer stem cells (LCSCs).

Methods: The hepatocellular carcinoma cell line Huh7 was used to separate CD90+ LCSCs by magnetic-activated cell sorting. CD90@TMs was characterized and their ability to target CD90+ LCSCs was determined. Experiments were used to investigate whether CD90@TMs combined with magnetic hyperthermia could effectively eliminate CD90+ LCSCs.

Results: The present study demonstrated that CD90+ LCSCs with stem cells properties were successfully isolated. We also successfully prepared CD90@TMs that was almost spherical and uniform with an average diameter of 130±4.6 nm and determined that magnetic iron oxide could be incorporated and retained a superparamagnetic response. CD90@TMs showed good targeting and increased inhibition of CD90+ LCSCs in vitro and in vivo compared to TMs.

Conclusions: CD90@TMs can be used for controlled and targeted delivery of anticancer drugs, which may offer a promising alternative for HCC therapy.

Keywords: CD90; LCSCs; TMs; hyperthermia therapy; targeting therapy.

MeSH terms

  • Animals
  • Antibodies / immunology*
  • Antibodies / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Immunomagnetic Separation / methods
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / metabolism
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / immunology*
  • Neoplastic Stem Cells / metabolism
  • Temperature
  • Thy-1 Antigens / immunology*
  • Thy-1 Antigens / metabolism
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antibodies
  • Thy-1 Antigens