Abstract
Cervical cancer presents extremely low PEDF expression which is associated with tumor progression and poor prognosis. In this study, folate receptor α (FRα)-targeted nano-liposomes (FLP) were designed to enhance the anti-tumor effect by targeting delivery of exogenous PEDF gene to cervical cancer cells. The targeting molecule F-PEG-Chol was firstly synthesized by a novel simpler method. FLP encapsulating PEDF gene (FLP/PEDF) with a typical lipid-membrane structure were prepared by a film dispersion method. The transfection experiment found FLP could effectively transfect human cervical cancer cells (HeLa cells). FLP/PEDF significantly inhibited the growth of HeLa cells and human umbilical vein endothelial cells (HUVEC cells) and suppressed adhension, invasion and migration of HeLa cells in vitro. In the abdominal metastatic tumor model of cervical cancer, FLP/PEDF administered by intraperitoneal injection exhibited a superior anti-tumor effect probably due to the up-regulated PEDF. FLP/PEDF could not only sharply reduce the microvessel density but also dramatically inhibit proliferation and markedly induce apoptosis of tumor cells in vivo. Moreover, the preliminary safety investigation revealed that FLP/PEDF had no obvious toxicity. These results clearly showed that FLP were desired carriers for PEDF gene and FLP/PEDF might represent a potential novel strategy for gene therapy of cervical cancer.
Highlights
Cervical cancer, called invasive cervical carcinoma, is the second malignant tumor to women all over the world[1]
We previously reported that PLGA nanoparticles significantly decreased HeLa cells adhesive rate at all the determined time points compared to control, PLP/ Pigment epithelium-derived factor (PEDF), folate-modified nano-liposomes (FLP)/PAAV2 and PLP/PAAV2. *p < 0.05. (B) Representative images of migrated HeLa cells derived from invasion assay and relative metastasis rates of HeLa cells
The targeting lipid F-PEG-Chol was expectably synthesized by a novel method, and folate receptor α (FRα)-targeted nano-lipoplexes loaded with PEDF gene (FLP/PEDF) were successfully developed by a film dispersion method for the first time
Summary
Cancer Cells Mediated by the Overreceived: 13 April 2016 accepted: 09 August 2016 Published: 31 August 2016 expressing FRα. Folate receptor α (FRα)-targeted nano-liposomes (FLP) were designed to enhance the anti-tumor effect by targeting delivery of exogenous PEDF gene to cervical cancer cells. 200 μL HeLa cells (2 × 105/mL in serum free RPMI-1640) transfected with nano-lipoplexes (PLP/PAAV2, FLP/PAAV2, PLP/PEDF and FLP/PEDF) were placed on the top chamber of each transwell (8 μm pore size, Corning, America) coated with 50 μL diluted Matrigel (volume ratio to RPMI-1640 serum-free was 1:3). Mice were injected intraperitoneally with 0.2 mL HeLa cells suspension (1 × 107 cells in serum free RPMI-1640) and randomly separated into five groups based on their body weights two days after inoculation They were administered once every third day with the nano-lipoplexes containing plasmid DNA (5 μg) in 200 μL volume. Differences were considered statistically significant at p < 0.05
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
