An aptamer-based drug delivery agent (CD133-apt-Dox) selectively and effectively kills liver cancer stem-like cells

Cancer Lett. 2021 Mar 31;501:124-132. doi: 10.1016/j.canlet.2020.12.022. Epub 2020 Dec 19.

Abstract

Liver cancer has no effective therapies, hence a poor survival. Cancer stem-like cells not only contribute to cancer initiation and progression, but also to drug resistance, cancer metastasis, and eventually treatment failure. Hence, any approaches that can effectively kill cancer stem-like cells hold a great potential for cancer treatment. CD133 is a robust marker for liver cancer stem-like cells. We developed a specific aptamer against CD133 (CD133-apt), and then loaded this aptamer with an anticancer drug doxorubicin (CD133-apt-Dox). The efficacy of CD133-apt-Dox in targeting liver cancer stem-like cells and its overall effect in treating liver cancer were investigated using multiple in vitro and in vivo studies including in patients-derived liver cancer organoids. We have observed that CD133-apt could preferably delivered doxorubicin to CD133-expressing cells with efficient drug accumulation and retention. CD133-apt-Dox impaired the self-renewal capacity of liver cancer stem-like cells and attenuated their stem-ness phenotypes in vitro or in vivo. CD133-apt-Dox significantly inhibited the growth of liver cancer cells and patients-derived organoids and reduced the growth of xenograft tumours in nude mice inhibited the growth of DEN-induced liver cancer in immunocompetent mice. Hence, aptamer-mediated targeting of CD133 is a highly promising approach for liver cancer therapy.

Keywords: Aptamer; CD133; Cancer stem-like cells; Hepatocellular carcinoma (HCC); Therapeutic targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen / genetics*
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Aptamers, Nucleotide / administration & dosage*
  • Aptamers, Nucleotide / genetics
  • Aptamers, Nucleotide / pharmacokinetics
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Drug Carriers / administration & dosage
  • Drug Carriers / pharmacokinetics
  • Drug Delivery Systems / methods
  • HEK293 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology

Substances

  • AC133 Antigen
  • Antibiotics, Antineoplastic
  • Aptamers, Nucleotide
  • Drug Carriers
  • Doxorubicin