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Analysis of Targeted Viral Protein Nanoparticles Delivered to HER2+ Tumors
11:52

Analysis of Targeted Viral Protein Nanoparticles Delivered to HER2+ Tumors

Published on: June 18, 2013

HER2-targeted doxorubicin-loaded cell-derived extracellular vesicles induce apoptosis of breast cancer cells via

Chan Mi Lee1,2, Do Sang Lee1,2, Ji Won Choi2

  • 1Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Cancer Cell International
|May 14, 2026
PubMed
Abstract

Insights

Engineered extracellular vesicles (EVs) targeted HER2-positive breast cancer, delivering doxorubicin (Dox) effectively. This peptide-mediated system enhanced tumor specificity and triggered apoptosis via the ROS/TXNIP pathway.

Area of Science:

  • Biomedical Engineering
  • Cancer Therapeutics
  • Nanotechnology

Background:

  • Conventional chemotherapy for HER2-positive breast cancer faces challenges with systemic toxicity and limited tumor selectivity.
  • Extracellular vesicles (EVs) offer biocompatible drug delivery, facilitating intercellular communication.
  • Engineering EVs with a HER2-binding peptide (P51) aims to improve doxorubicin (Dox) targeting and efficacy.

Purpose of the Study:

  • To develop a peptide-mediated targeted delivery system using engineered EVs for doxorubicin (Dox) in HER2-positive breast cancer.
  • To enhance tumor specificity and apoptotic efficacy of Dox delivery.
  • To investigate the molecular mechanisms underlying EV-mediated drug delivery and cancer cell apoptosis.

Main Methods:

  • HEK-293 cells were transfected to generate EVs displaying the P51 peptide.
  • Dox was loaded into P51-displaying EVs to create P51-EVDox.
  • In vitro and in vivo studies utilized HER2-overexpressing BT-474 cells to evaluate cellular uptake, antitumor efficacy, and apoptosis-related markers (cleaved caspase-3, PARP cleavage, p53) via RNA sequencing.

Main Results:

  • P51-EVDox demonstrated superior binding and intracellular accumulation in HER2-positive cells compared to non-targeted EV-Dox.
  • Transcriptomic analysis revealed significant upregulation of thioredoxin-interacting protein (TXNIP) in cells treated with P51-EVDox.
  • Increased activation of apoptosis markers (cleaved caspase-3, PARP cleavage, p53) indicated a ROS/TXNIP-driven apoptotic cascade.

Conclusions:

  • Peptide-functionalized EVs serve as a promising platform for targeted chemotherapy in HER2-positive breast cancer.
  • P51-EVDox integrates ligand-mediated recognition with EV-based Dox delivery for enhanced tumor suppression.
  • The study highlights the activation of the ROS/TXNIP signaling pathway, leading to increased apoptosis and tumor suppression.
Keywords:
ApoptosisExtracellular vesicles (EVs)HER2-positive breast cancerPeptide-engineered EVsROS/TXNIP pathway

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