Retro-inverso follicle-stimulating hormone peptide-mediated polyethylenimine complexes for targeted ovarian cancer gene therapy

Drug Delivery

Jing Wang¹  Ran Zhao¹  Yi Yu¹  Haiyan Tai¹  Mengyu Zhang²  Congjian Xu³  Mingxing Zhang³  Xiaoyan Zhang³  Qingqing Cai³ 

[1]Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China

[2]Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China

[3]Department of Gynecology, 411 Military Hospital Affiliated to Changhai Hospital of Shanghai, Shanghai, China

[4]Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, Chin

[5]Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China

[6]Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, Chin

关键词: Ovarian carcinoma;    targeted therapy;    follicle-stimulating hormone;    growth-regulated oncogene α;    RNA interference;    nanoparticle;   

DOI  :  10.1080/10717544.2018.1461956

来源: publisher

【 摘 要 】

Background: The development of nanoparticle drug delivery systems with targeted ligands has the potential to increase treatment efficiency in ovarian cancer.Methods: We developed a 21-amino acid peptide, YTRDLVYGDPARPGIQGTGTF (L-FP21) conjugated to polyethylenimine (PEI) and methoxy polyethylene glycol (mPEG) to prepare a nanoparticle drug vehicle to target follicle-stimulating hormone receptor (FSHR) in ovarian cancer. At the same time, we optimized the ligand of the nanoparticle vehicle using D-peptides, which consist of D-amino acids (D-FP21). Nanoparticle vehicles carrying the therapeutic gene plasmid growth-regulated oncogene alpha (pGRO-α) short hairpin RNA (shRNA) (FP21-PEG-PEI/pGRO-α) were prepared for further investigation.Results: Compared with L-FP21, D-FP21 exhibited improved biological stability and higher uptake rate for FSHR-expressing ovarian cancer cells. The cytotoxicity of the L, D-FP21-PEG-PEI/pGRO-α complexes were significantly lower than that of the PEI/pGRO-α complex. The nanoparticle drug with the targeted ligand showed higher transfection efficiencies and improved anti-proliferation effects for ovarian cancer cells than that without the targeted ligand (mPEG-PEI/pGRO-α). Furthermore, an in vivo evaluation of an antitumor assay indicated that D-FP21-PEG-PEI/pGRO-α inhibited the growth of tumor spheroids considerably more than L-FP21-PEG-PEI/pGRO-α; their tumor inhibition rates were 58.5% and 33.3%, respectively.Conclusions: D-FP21-PEG-PEI/plasmid DNA is a safe and efficient gene delivery vehicle for ovarian cancer targeted therapy.

【 授权许可】

CC BY