scholarly journals Folate Receptor Targeted Delivery of siRNA and Paclitaxel to Ovarian Cancer Cells via Folate Conjugated Triblock Copolymer to Overcome TLR4 Driven Chemotherapy Resistance

2015 ◽  
Vol 17 (1) ◽  
pp. 76-87 ◽  
Author(s):  
Steven K. Jones ◽  
Vincent Lizzio ◽  
Olivia M. Merkel
Nano LIFE ◽  
2018 ◽  
Vol 08 (01) ◽  
pp. 1850001 ◽  
Author(s):  
Shibin Du ◽  
Yunfei Wang ◽  
Junping Ao ◽  
Kai Wang ◽  
Zhiying Zhang ◽  
...  

Ovarian cancer is the highest mortality rate of all cancers in the female reproductive system. Over the past decades, small interfering RNA (si RNA) has been explored as a promising therapeutic candidate for gene therapy. However, its clinical application is limited by the lack of safe and efficient methods for gene delivery. Graphene oxide (GO) was modified with polyethylene glycol (PEG), polyethylenimine (PEI) and folic acid (FA), for targeted delivery of small interfering RNA (siRNA) that inhibits ovarian cancer cell growth, and the efficacy of such complex was evaluated by a series of in vitro experiments. The synthesized vehicle PEG-GO-PEI-FA was characterized by atomic force microscopy (AFM), Malvern particle size analyzer, UV-visible spectroscopy and Fourier transform infrared spectroscopy (FTIR), and the results showed that PEG, PEI and FA could be covalently grafted to GO surface, forming PEG-GO-PEI-FA particles with a size of [Formula: see text][Formula: see text]nm and a potential of 14.7[Formula: see text]mV. Agarose-gel electrophoresis demonstrated that siRNA can be adsorbed onto the surface of PEG-GO-PEI-FA by electrostatic interaction. Laser confocal microscopy demonstrated that siRNA-adsorbed PEG-GO-PEI-FA could be target into folate receptor (FR)-overexpressing ovarian cancer cells. Compared to the PEG-GO-PEI/siRNA without folate modification, PEG-GO-PEI-FA/siRNA showed more pronounced inhibitory effect on growth of ovarian cancer cells. In conclusion, we have successfully synthesized a vector that is safe, efficient and specific to target tumor cell for gene delivery.


Biomaterials ◽  
2014 ◽  
Vol 35 (14) ◽  
pp. 4297-4309 ◽  
Author(s):  
Yunfei Wang ◽  
Jinhua Zhou ◽  
Lihua Qiu ◽  
Xinran Wang ◽  
Lilan Chen ◽  
...  

2013 ◽  
Vol 9 (5) ◽  
pp. 833-844 ◽  
Author(s):  
Zhiyao He ◽  
Yiyi Yu ◽  
Ying Zhang ◽  
Yongdong Yan ◽  
Yu Zheng ◽  
...  

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Xi Zhang ◽  
Guoqing Hou ◽  
Andong Liu ◽  
Hui Xu ◽  
Yang Guan ◽  
...  

Abstract Ovarian cancer remains the most lethal gynecologic malignancy with late detection and acquired chemoresistance. Advanced understanding of the pathophysiology and novel treatment strategies are urgently required. A growing body of proteomic investigations suggest that phosphorylation has a pivotal role in the regulation of ovarian cancer associated signaling pathways. Matrine has been extensively studied for its potent anti-tumor activities. However, its effect on ovarian cancer cells and underlying molecular mechanisms remain unclear. Herein we showed that matrine treatment inhibited the development and progression of ovarian cancer cells by regulating proliferation, apoptosis, autophagy, invasion and angiogenesis. Matrine treatment retarded the cancer associated signaling transduction by decreasing the phosphorylation levels of ERK1/2, MEK1/2, PI3K, Akt, mTOR, FAK, RhoA, VEGFR2, and Tie2 in vitro and in vivo. Moreover, matrine showed excellent antitumor effect on chemoresistant ovarian cancer cells. No obvious toxic side effects were observed in matrine-administrated mice. As the natural agent, matrine has the potential to be the targeting drug against ovarian cancer cells with the advantages of overcoming the chemotherapy resistance and decreasing the toxic side effects.


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