Triphenyl phosphonium functionalized amphiphilic peptides as promising antibacterial and anticancer agents

Tanushree Mondal1, Sraddhya Roy2, Ananya Das2

  • 1School of Biological Sciences, Indian Association for the Cultivation of Science, A2A & 2B Raja S. C. Mullick Road, Jadavpur, Kolkata-700032, India. bcab@iacs.res.in.

Chemical Communications (Cambridge, England)
|May 8, 2025
PubMed

Insights

Triphenyl phosphonium conjugated amphiphilic peptides self-assemble into micelles with potential antimicrobial activity. These peptides also destroy ovarian cancer cells by generating reactive oxygen species (ROS), showing promise as dual-action biomaterials.

Area of Science:

  • Biomaterials Science
  • Medicinal Chemistry
  • Nanotechnology

Background:

  • Drug-resistant microbial strains pose a significant global health threat.
  • Ovarian cancer remains a challenging malignancy with limited treatment options.
  • Developing novel therapeutic agents with dual antimicrobial and anticancer properties is highly desirable.

Purpose of the Study:

  • To synthesize and characterize triphenyl phosphonium conjugated amphiphilic peptides.
  • To investigate the self-assembly behavior of these peptides into micelles.
  • To evaluate the antimicrobial and anticancer potential of the peptide-based micelles.

Main Methods:

  • Peptide synthesis and conjugation with triphenyl phosphonium.
  • Micelle formation and characterization using dynamic light scattering.
  • Antimicrobial activity assays against drug-resistant bacterial strains.
  • Ovarian cancer cell line treatment and assessment of cytotoxicity.
  • Mitochondrial reactive oxygen species (ROS) generation measurement.
  • Cytocompatibility testing with non-cancerous HEK 293 cells.

Main Results:

  • Triphenyl phosphonium conjugated amphiphilic peptides successfully self-assembled into stable micelles.
  • The peptide micelles exhibited significant antimicrobial activity against multidrug-resistant strains.
  • These micelles effectively induced apoptosis in ovarian cancer cells.
  • Mitochondrial ROS generation was identified as the primary mechanism for cancer cell death.
  • The peptide micelles demonstrated excellent cytocompatibility with normal HEK 293 cells.

Conclusions:

  • Triphenyl phosphonium conjugated amphiphilic peptides form self-assembled micelles with potent dual therapeutic potential.
  • These novel biomaterials offer a promising strategy for combating drug-resistant infections and treating ovarian cancer.
  • The selective toxicity towards cancer cells highlights their potential as targeted therapeutic agents.