Follicle stimulating hormone receptor mediated gene delivery to target ovarian carcinoma in vitro

Donga, Chris; Chen, Jun; Zhang, Xiaoyan; Xu, Congjian

doi:10.5372/1905-7415.0602.045

Abstract

Background: How to deliver sufficient therapeutic genes into cancer cells while causing fewer side effects are major challenges in cancer gene therapies. Receptor mediated gene delivery enables specific delivering therapeutic genes into target cancer cells and increases the efficacy.

Objectives: We developed a novel receptor mediated short interference RNA (siRNA) expression plasmid delivery system against ovarian carcinoma cells with improved biocompatibility in vitro.

Methods: Follice stimulating hormone (FSH) peptide (β: 33-55) was grafted to polyethylenimine (PEI) via a bifunctional polyethylene glycol (PEG) and complexed with anti chemokine c-x-c motif ligand 1 (CXCL1) plasmid DNA (pDNA) to form FSH-PEG-PEI/pDNA polyplexes at various N/P ratios. The cytotocity, transfection efficiency, and CXCL1 silencing effect were evaluated respectively.

Results: The FSH-PEG-PEI/pDNA polyplexes showed low cytotoxicity, high transfection efficiency, and specific CXCL1 gene silencing effect. The 2% FSH-PEG-PEI conjugate complexed with pDNA at N/P ratio of 25 has better physicochemical properties. The therapeutic siRNA expression plasmid uptake by follice stimulating hormone receptor (FSHR) expression ovarian carcinoma cells was through a receptor-mediated manner.

Conclusion: The FSH-PEG-PEI conjugate can be used as a novel receptor mediated gene delivery system against ovarian carcinomas. This strategy could be extended to a wide range of targeted gene therapeutics against different cancers.

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Follicle stimulating hormone receptor mediated gene delivery to target ovarian carcinoma in vitro

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