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Int. J. Mol. Sci. 2017, 18(4), 813; doi:10.3390/ijms18040813

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

1
Zoology Department, Faculty of Sciences, Mansoura University, Mansoura 35516, Egypt
2
Center for Materials Science, Zewail City of Science and Technology, Cairo 12588, Egypt
3
Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
4
Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
5
Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt
6
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Yogesh Kumar Vashist
Received: 7 February 2017 / Revised: 16 March 2017 / Accepted: 24 March 2017 / Published: 12 April 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
View Full-Text   |   Download PDF [2951 KB, uploaded 12 April 2017]   |  

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. View Full-Text
Keywords: PLGA; drug delivery system; paclitaxel; ovarian cancer stem cells; nude mice PLGA; drug delivery system; paclitaxel; ovarian cancer stem cells; nude mice
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Abou-ElNaga, A.; Mutawa, G.; El-Sherbiny, I.M.; Abd-ElGhaffar, H.; Allam, A.A.; Ajarem, J.; Mousa, S.A. Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells after Xenograft into Nude Mice. Int. J. Mol. Sci. 2017, 18, 813.

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