Antitumor effect of lonidamine-polypeptide-peptide nanoparticles in breast cancer models

Ifat Cohen-Erez, Carol Issacson, Yael Lavi, Ruthy Shaco-Levy, Jammi Milam, Brenda Laster, Levi A. Gheber, Hanna Rapaport

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Biomaterials folded into nanoparticles (NPs) can be utilized as targeted drug delivery systems for cancer therapy. NPs may provide a vehicle for the anticancer drug lonidamine (LND), which inhibits glycolysis but was suspended from use at the clinical trial stage because of its hepatotoxicity due to poor solubility and pharmacokinetic properties. The NPs prepared by coassembly of the anionic polypeptide poly gamma glutamic acid (γ-PGA) and a designed amphiphilic and positively charged peptide (designated as mPoP-NPs) delivered LND to the mitochondria in cell cultures. In this study, we demonstrate that LND-mPoP-NP effective drug concentrations can be increased to reach therapeutically relevant concentrations. The self-Assembled NP solution was subjected to snap-freezing and lyophilization and the resultant powder was redissolved in a tenth of the original volume. The NP size and their ability to target the proximity of the mitochondria of breast cancer cells were both maintained in this new formulation, C-LND-mPoP-NPs. Furthermore, these NPs exhibited 40% better cytotoxicity, relative to the nonlyophilized LND-mPoP-NPs and led to tumor growth inhibition with no adverse side effects upon intravenous administration in a xenograft breast cancer murine model.

Original languageEnglish
Pages (from-to)32670-32678
Number of pages9
JournalACS applied materials & interfaces
Volume11
Issue number36
DOIs
StatePublished - 11 Sep 2019

Keywords

  • breast cancer
  • intracellular drug delivery
  • lonidamine
  • mitochondria
  • peptides
  • self-Assembled nanoparticles

ASJC Scopus subject areas

  • Materials Science (all)

Fingerprint

Dive into the research topics of 'Antitumor effect of lonidamine-polypeptide-peptide nanoparticles in breast cancer models'. Together they form a unique fingerprint.

Cite this