Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

Technol Cancer Res Treat. 2021 Jan-Dec:20:15330338211027898. doi: 10.1177/15330338211027898.

Abstract

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

Keywords: NKA-α1; breast cancer; epirubicin; peptide; targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Epirubicin / administration & dosage
  • Epirubicin / pharmacology*
  • Epithelial Cells
  • Female
  • Humans
  • Liposomes
  • Mice
  • Nanoconjugates*
  • Phosphatidylethanolamines*
  • Polyethylene Glycols*
  • Sodium-Potassium-Exchanging ATPase / metabolism*

Substances

  • 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)
  • Antibiotics, Antineoplastic
  • Liposomes
  • Nanoconjugates
  • Phosphatidylethanolamines
  • Polyethylene Glycols
  • Epirubicin
  • ATP1A1 protein, human
  • Atp1a1 protein, mouse
  • Sodium-Potassium-Exchanging ATPase