A chemo/chemodynamic nanoparticle based on hyaluronic acid induces ferroptosis and apoptosis for triple-negative breast cancer therapy

Carbohydr Polym. 2024 Apr 1:329:121795. doi: 10.1016/j.carbpol.2024.121795. Epub 2024 Jan 9.

Abstract

Triple-negative breast cancer (TNBC) poses a serious threat to women's life and health due to its high malignancy, strong invasiveness, and propensity for early recurrence and metastasis. Therefore, there is an urgent need to develop a highly effective and low-toxic TNBC treatment scheme to enhance the anti-cancer efficacy and prolong the survival of patients. In this work, we designed and synthesized a chemodynamic therapy (CDT) agent (HA-Fc-Mal). The chemo/chemodynamic (CT/CDT) nanoparticle (HCM@DOX) based on hyaluronic acid induces ferroptosis and apoptotic for TNBC therapy was constructed via self-assembled of HA-Fc-Mal and doxorubicin (DOX). HCM@DOX orderly realized the TNBC targeting, controlled DOX release, GSH depletion and induce ROS erupt. In vivo and in vitro experiments confirmed that HCM@DOX inhibited the growth of 4 T1 tumors through ferroptosis and apoptosis, and the tumor inhibition rate was as high as 81.87 %. In addition, HCM@DOX significantly inhibited lung metastasis and exhibited excellent biosafety. Overall, our findings offer a new strategy for TNBC therapy using a CT/CDT nanoparticle that induces ferroptosis and apoptosis.

Keywords: Chemo/chemodynamic therapy; Controlled drugs release; Ferroptosis/apoptosis; Hyaluronic acid; TNBC.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Female
  • Ferroptosis*
  • Humans
  • Hyaluronic Acid / pharmacology
  • Nanoparticles*
  • Triple Negative Breast Neoplasms* / drug therapy

Substances

  • Hyaluronic Acid
  • Doxorubicin