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Novel Ran-RCC1 Inhibitory Peptide-Loaded Nanoparticles Have Anti-Cancer Efficacy In Vitro and In Vivo

Yusuf A Haggag1,2, Kyle B Matchett3, Robert A Falconer4

  • 1Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Tanta, Tanta 31111, Egypt. youssif.hagag@pharm.tanta.edu.eg.

Cancers
|February 17, 2019
PubMed

Insights

Novel peptides targeting Ras protein-Regulator of chromosome condensation 1 (Ran) were encapsulated in nanoparticles for cancer therapy. These peptide-loaded nanoparticles demonstrated significant antitumor and anti-metastatic effects in breast and lung cancer models.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Effective delivery of anticancer agents to subcellular targets remains a challenge in cancer therapy.
  • Peptides offer potential as selective, potent therapeutics with low toxicity to normal cells.
  • Ras protein-Regulator of chromosome condensation 1 (Ran) is a novel therapeutic target in breast cancer.

Purpose of the Study:

  • To develop and evaluate novel Ran-inhibitory peptides encapsulated in polyethylene glycol-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles for cancer treatment.
  • To assess the anticancer and anti-metastatic efficacy of these peptide-loaded nanoparticles in vitro and in vivo.

Main Methods:

  • A modified double emulsion solvent evaporation technique was used to create optimized peptide-loaded PEG-PLGA nanoparticles.
  • In vitro studies utilized Ran-expressing breast (MDA-MB-231) and lung (A549) cancer cell lines.
  • In vivo efficacy was evaluated in Solid Ehrlich Carcinoma-bearing mice, alongside migration, invasion, and colony formation assays.

Main Results:

  • PEG-PLGA nanoparticles encapsulating an N-terminal peptide exhibited significant antitumor activity against breast and lung cancer cells in vitro.
  • These nanoparticles demonstrated pronounced anti-metastatic effects in vitro.
  • In vivo studies showed a significant reduction in tumor volume and growth inhibition in a breast cancer model.

Conclusions:

  • Novel Ran-inhibitory peptides effectively delivered via PEG-PLGA nanoparticles show significant potential for cancer therapy.
  • This Ran-targeting peptide construct demonstrates promise for treating breast cancer and other Ran-overexpressing cancers.
  • The developed nanoparticles offer an effective strategy for delivering therapeutic peptides to cancer cells.
Keywords:
RanRan-RCC1 peptideanti-canceranti-metastaticbreast cancerdrug deliverylung cancernanoparticle

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