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Conferring receptors on recipient cells with extracellular vesicles for targeted drug delivery

Zachary Quinn1, Wenjun Mao2, Yiqiu Xia3

  • 1The Pq Laboratory of Micro/Nano BiomeDx, Department of Biomedical Engineering, Binghamton University-SUNY, Binghamton, NY, 13902, United States.

Bioactive Materials
|October 7, 2020
PubMed

Insights

This study enhances triple negative breast cancer (TNBC) treatment by engineering HER2-expressing TNBC cells. Targeted drug delivery to these modified cells improved therapeutic efficacy in vitro and in vivo.

Area of Science:

  • Biomedical Engineering
  • Oncology
  • Nanotechnology

Background:

  • Triple negative breast cancer (TNBC) lacks effective targeted therapies due to absent hormone receptors and HER2.
  • Current TNBC treatments show limited efficacy, necessitating novel therapeutic strategies.
  • Modulating tumor microenvironments and antigen presentation can enhance anti-tumor immune responses.

Purpose of the Study:

  • To develop a method for enhancing TNBC targeting and treatment efficacy.
  • To investigate the potential of extracellular vesicle (EV)-mediated membrane fusion for antigen presentation.
  • To evaluate the effectiveness of HER2-targeted drug delivery in modified TNBC cells.

Main Methods:

  • Engineered TNBC cells (MDA-MB-231) by fusing HER2+ extracellular vesicles (EVs) from BT-474 cells to display HER2.
  • Utilized anti-HER2 antibody conjugated paclitaxel-loaded liposomes for targeted drug delivery.
  • Assessed treatment efficacy both in vitro and in vivo.

Main Results:

  • Successfully conferred HER2 expression onto the surface of TNBC cells via EV-plasma membrane fusion.
  • Demonstrated improved treatment efficacy of HER2-targeted paclitaxel delivery in modified TNBC.
  • Showcased enhanced therapeutic outcomes in both in vitro and in vivo models.

Conclusions:

  • EV-mediated membrane fusion is a facile method to alter cell surface antigen presentation in TNBC.
  • HER2 grafting combined with targeted drug delivery significantly improves TNBC treatment efficacy.
  • This approach holds promise for advancing targeted therapy and immunotherapy for TNBC.
Keywords:
Drug deliveryExtracellular vesiclesHER2Triple-negative breast cancer

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