Novel Nano-therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells after Xenograft into Nude Mice

Journal Article
Mousa, Amoura Abou-ElNaga, Ghada Mutawa, Ibrahim M. El-Sherbiny, Hassan Abd-ElGhaffar, Ahmed A. Allam, Jamaan Ajarem and Shaker A. . 2017
Publication Work Type: 
paper
Magazine \ Newspaper: 
International Journal of Molecular Sciences (Impact factor: 3.25)
Publication Abstract: 

The power of tumorigenesis, chemo-resistance and metastasis in malignant ovarian
tumors resides in a tiny population of cancer cells known as ovarian cancer stem cells (OCSCs).
Developing nano-therapeutic targeting of OCSCs is considered a great challenge. The potential use
of poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) was investigated as a drug delivery system
for paclitaxel (PTX) against OCSCs in vitro and in vivo. PTX-loaded PLGA NPs were prepared
by an emulsion solvent evaporation method, supported by incorporation of folic acid (FA) as the
ligand. NPs were characterized for size, surface morphology, drug loading, and encapsulation
efficiency. In vitro cytotoxicity of PTX-loaded FA/PLGA NPs was tested against OCSCs with MTT
assay. In vivo anti-tumoral efficiency and active targeting potential of prepared NPs against tumors
in nude mice were investigated. In vitro results revealed that IC50 of PTX was significantly reduced
after loading on PLGA NPs. On the other hand, in vivo results showed that PLGA NPs enhanced
the tumor suppression efficiency of PTX. Investigation with real time quantitative PCR analysis
revealed the limiting expression of chemo-resistant genes (ABCG2 and MDR1) after applying PLGA
NPs as a drug delivery system for PTX. Histopathological examination of tumors showed the
effective biological influence of PTX-loaded FA/PLGA NPs through the appearance of reactive
lymphoid follicles. Targeting potential of PTX was activated by FA/PLGA NPs through significant
preservation of body weight (p < 0.0001) and minimizing the systemic toxicity in healthy tissues.
Immunohistochemical investigation revealed a high expression of apoptotic markers in tumor tissue,
supporting the targeting effect of FA/PLGA NPs. A drug delivery system based on FA/PLGA NPs
can enhance PTX’s in vitro cytotoxicity and in vivo targeting potential against OCSCs.

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