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Poly(l-Ornithine)-Based Polymeric Micelles as pH-Responsive Macromolecular Anticancer Agents.

Miao Pan1,2,3, Chao Lu4, Wancong Zhang1,2,3

  • 1Plastic Surgery Institute of Shantou University Medical College, Shantou 515041, China.

Pharmaceutics
|April 28, 2023
PubMed
Summary

New anticancer polymers, poly(l-ornithine)-b-poly(l-phenylalanine) (PLO-b-PLF), show promise for tumor treatment. Modified versions exhibit reduced toxicity and targeted cancer cell destruction via charge reversal in acidic tumor environments.

Keywords:
anticancer peptidemembrane lysispH-responsivepoly(l-ornithine)

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Area of Science:

  • Biomaterials Science
  • Polymer Chemistry
  • Cancer Therapeutics

Background:

  • Anticancer peptides and polymers offer a novel approach to combatting multidrug resistance in cancer treatment.
  • Block copolypeptides can self-assemble into nanostructures for targeted drug delivery and interaction with cancer cells.

Purpose of the Study:

  • To prepare and evaluate poly(l-ornithine)-b-poly(l-phenylalanine) (PLO-b-PLF) block copolypeptides as macromolecular anticancer agents.
  • To modify PLO-b-PLF to reduce systemic cytotoxicity while retaining tumor-specific anticancer activity.

Main Methods:

  • Synthesis of amphiphilic PLO-b-PLF block copolypeptides.
  • Characterization of self-assembly into nanosized polymeric micelles in aqueous solution.
  • Modification of PLO-b-PLF with 1,2-dicarboxylic-cyclohexene anhydride (DCA) to create PLO(DCA)-b-PLF, introducing an acid-labile linkage.

Main Results:

  • Amphiphilic PLO-b-PLF formed stable nanosized micelles that interacted electrostatically with cancer cells, leading to membrane lysis.
  • The modified anionic PLO(DCA)-b-PLF exhibited negligible hemolysis and cytotoxicity under physiological conditions.
  • Upon exposure to a weakly acidic tumor microenvironment, PLO(DCA)-b-PLF underwent charge reversal, recovering its potent anticancer activity.

Conclusions:

  • PLO-based polypeptides demonstrate potential as drug-free anticancer agents.
  • The charge-reversal strategy effectively mitigates systemic toxicity while enabling targeted cancer cell destruction.
  • These findings support the development of PLO-based polypeptides for innovative tumor treatment strategies.