Selectively Suppressing Tumor Angiogenesis for Targeted Breast Cancer Therapy by Genetically Engineered Phage

Yan Li1, Xuewei Qu1, Binrui Cao1

  • 1Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, Institute for Biomedical Engineering, Science and Technology, University of Oklahoma, 101 Stephenson Parkway, Norman, OK, 73019-5300, USA.

Insights

Engineered bacteriophage (phage) nanoparticles target breast tumors by binding angiogenin, a protein crucial for tumor growth. This novel approach offers targeted cancer therapy with potential for broad application.

Area of Science:

  • Biotechnology
  • Nanomedicine
  • Oncology

Background:

  • Antiangiogenesis therapy shows promise for cancer treatment but lacks tumor-homing capabilities.
  • Angiogenin, a tumor-secreted protein driving angiogenesis, remains an unexplored therapeutic target.
  • Current antiangiogenic agents lack specificity and tumor-homing properties.

Purpose of the Study:

  • To engineer bacteriophage (phage) nanoparticles for targeted cancer therapy.
  • To develop a system that homes to tumors and inhibits angiogenesis by targeting angiogenin.
  • To create a universal, plug-and-play therapeutic platform for various cancers.

Main Methods:

  • Genetic engineering of filamentous fd phage to display angiogenin-binding peptides and tumor-homing peptides.
  • Utilizing phage display technology to discover and customize tumor-homing peptides for specific cancers.
  • Developing phage nanoparticles capable of binding angiogenin and preventing tumor angiogenesis.

Main Results:

  • Engineered phage nanoparticles demonstrated tumor-homing capabilities to orthotopic breast tumors.
  • The phage nanoparticles successfully captured angiogenin, inhibiting tumor angiogenesis.
  • The developed phage system functions as a universal therapeutic agent adaptable to different cancer types.

Conclusions:

  • Engineered bacteriophages represent a novel, biocompatible nanofiber platform for targeted cancer therapy.
  • This approach overcomes the limitations of current antiangiogenic agents by incorporating tumor-homing and angiogenin-binding functionalities.
  • The "plug-and-play" nature of the phage system allows for customization against diverse cancers, offering a versatile therapeutic strategy.