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Eur J Cell Biol. 2017 Sep;96(6):600-611. doi: 10.1016/j.ejcb.2017.04.005. Epub 2017 May 10.

Cancer cell death induced by nanomagnetolectin.

Author information

1
Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt.
2
Department of Biochemistry, Faculty of Agriculture, Zagazig University, Zagazig 44511, Egypt.
3
Department of Pharmacology and Toxicology, Faculty of Pharmacy and Drug Manufacturing, Pharos University, Alexandria 21311, Egypt.
4
Department of Physiology, Biochemistry, and Pharmacology, King Faisal University, 31982, Al-Hasa, Saudi Arabia; Department of Biochemistry, Faculty of Veterinary Medicine, Alexandria University, Egypt.
5
Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
6
Institute of General Genetics and Cytology, Almaty 050060, Kazakhstan.
7
Department of Biomedical Engineering, Florida International University, Miami FL 33174, USA.
8
GlycoMantra, Inc., Baltimore MD 21227, USA. Electronic address: hfzahmed86@gmail.com.

Abstract

Magnetic nanoparticles represent a new paradigm for molecular targeting therapy in cancer. However, the transformative targeting potential of magnetic nanoparticles has been stymied by a key obstacle-safe delivery to specified target cells in vivo. As cancer cells grow under nutrient deprivation and hypoxic conditions and decorate cell surface with excessive sialoglycans, sialic acid binding lectins might be suitable for targeting cancer cells in vivo. Here we explore the potential of magnetic nanoparticles functionalized with wheat germ lectin (WGA) conjugate, so-called nanomagnetolectin, as apoptotic targetable agents for prostate cancer. In the presence of magnetic field (magnetofection) for 15min, 2.46nM nanomagnetolectin significantly promoted apoptosis (∼12-fold, p value <0.01) of prostate cancer cells (LNCaP, PC-3, DU-145) compared to normal prostate epithelial cells (PrEC, PNT2, PZ-HPV-7), when supplemented with 10mM sialic acid under nutrient deprived condition. Nanomagnetolectin targets cell-surface glycosylation, particularly sialic acid as nanomagnetolectin induced apoptosis of cancer cells largely diminished (only 2 to 2.5-fold) compared to normal cells. The efficacy of magnetofected nanomagnetolectin was demonstrated in orthotopically xenografted (DU-145) mice, where tumor was not only completely arrested, but also reduced significantly (p value <0.001). This was further corroborated in subcutaneous xenograft model, where nanomagnetolectin in the presence of magnetic field and photothermal heating at ∼42°C induced apoptosis of tumor by ∼4-fold compared to tumor section heated at ∼42°C, but without magnetic field. Taken all together, the study demonstrates, for the first time, the utility of nanomagnetolectin as a potential cancer therapeutic.

KEYWORDS:

Apoptosis; Cell metabolism; Glycosylation sensing; Magnetofection; Metabolic glycoengineering; Nanomagnetolectin; Nanoparticles; Nutrient deprivation; Sialic acid; Wheat germ agglutinin

PMID:
28521959
PMCID:
PMC5610079
DOI:
10.1016/j.ejcb.2017.04.005
[Indexed for MEDLINE]
Free PMC Article

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