JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Nanoconjugate Carrying pH-Responsive Transferrin Receptor-Targeted Hesperetin Triggers Triple-Negative Breast Cancer Cell Death through Oxidative Attack and Assemblage of Pro-Apoptotic Proteins

  • 0Biochemistry, Molecular Endocrinology and Reproductive Physiology Laboratory, Department of Human Physiology, Vidyasagar University, Midnapore, West Bengal, India, 721102.
Acs Applied Bio Materials +

|

November 6, 2024

|

November 6, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Researchers developed targeted nanoparticles carrying hesperetin (HSP) to treat aggressive triple-negative breast cancer (TNBC). These PLGA-HSP-TF NPs effectively kill TNBC cells via oxidative stress and apoptosis, showing promise for cancer therapy.

Area Of Science

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Research

Background

  • Triple-negative breast cancer (TNBC) is aggressive and resistant to current treatments.
  • Hesperetin (HSP), a natural flavonoid, shows anticancer potential but is limited by poor solubility.
  • Targeted drug delivery systems are needed to improve HSP efficacy for TNBC.

Purpose Of The Study

  • To fabricate and characterize a pH-responsive, transferrin receptor-targeted nanobioconjugate of hesperetin (HSP) loaded poly(lactic-co-glycolic acid) (PLGA).
  • To evaluate the in vitro and in vivo anticancer efficacy of the developed PLGA-HSP-TF NPs against triple-negative breast cancer.

Main Methods

  • Synthesis and characterization of PLGA nanoparticles (NPs), PLGA-HSP NPs, and PLGA-HSP-TF NPs using DLS, FTIR, FE-SEM, and 1H NMR.
  • Assessment of nanoparticle stability, in vitro drug release, cytotoxicity, oxidative stress, apoptosis, and cell cycle arrest.
  • In vivo studies involving tumor regression and host survival in Ehrlich ascites carcinoma (EAC) bearing mice.

Main Results

  • PLGA-HSP-TF NPs demonstrated pH-dependent intracellular release of HSP in MDA-MB-231 cells.
  • HSP release induced excessive reactive oxygen species (ROS), leading to oxidative stress, mitochondrial dysfunction, and apoptosis.
  • Significant in vivo tumor regression and improved host survival were observed with PLGA-HSP-TF NPs compared to free HSP, with minimal toxicity.

Conclusions

  • PLGA-HSP-TF NPs are a stable, biocompatible, and targeted drug delivery system for hesperetin.
  • The developed nanobioconjugate effectively induces oxidative stress and apoptosis in TNBC cells.
  • PLGA-HSP-TF NPs represent a promising nanotherapeutic candidate for aggressive triple-negative breast cancer treatment.

Keywords: