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A helical oncolytic polypeptide with potent membranolytic activity for cancer therapy

Xue Hu1, Jie Li2, Yuhao Zhang2

  • 1School of Medicine, South China University of Technology, Guangzhou 510006, China. yuanyy@scut.edu.cn.

Biomaterials Science
|January 5, 2023
PubMed

Insights

A new cationic helical oncolytic polypeptide (OLPP) effectively combats multidrug-resistant cancer cells by directly lysing cell membranes. This protease-resistant peptide suppressed tumor growth in mice, showing potential as an oncolytic chemotherapeutic.

Area of Science:

  • Biochemistry
  • Materials Science
  • Oncology

Background:

  • Oncolytic peptides (OLPs) with membranolytic activity offer promise against multidrug-resistant cancers.
  • Developing novel OLPs with enhanced stability and efficacy is crucial for cancer therapy.

Purpose of the Study:

  • To synthesize and characterize a novel cationic helical oncolytic polypeptide (OLPP).
  • To evaluate the membranolytic activity, cytotoxicity, and in vivo efficacy of the OLPP for cancer treatment.

Main Methods:

  • The OLPP was synthesized using ring-opening polymerization of N-carboxyanhydrides (NCAs) and thiol-ene reactions.
  • Protease resistance, cytotoxicity against various cancer cell lines, and mechanism of cell death were assessed.
  • In vivo tumor suppression was evaluated following intra-tumoral injection in mice.

Main Results:

  • The synthesized OLPP demonstrated significant protease resistance.
  • High cytotoxicity was observed against a panel of cancer cell lines, inducing necrosis via direct membrane lysis.
  • Intra-tumoral administration of OLPP effectively inhibited tumor growth in vivo.

Conclusions:

  • The cationic helical oncolytic polypeptide (OLPP) exhibits potent membranolytic activity and direct oncolytic effects.
  • OLPP shows promise as a novel chemotherapeutic agent for combating multidrug-resistant cancers.
  • The synthesized OLPP represents a potential advancement in oncolytic peptide-based cancer therapy.

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