Preparation and identification of folate-targeting liver cancer phase-transition nanoparticles carrying suicide gene / 肿瘤

ABSTRACT

Objective: To develop the folic acid (FA)-targeting poly (lactic-co-glycolic acid) (PLGA) phase-transition nanoparticles loaded with herpes simplex virus type(HSV1)-thymidine kinase (TK) suicide gene and perfluoropentane (PFP) (named as FA-PLGA/PFP-TK), as well as to identify the targeting performance, enhancement effect of ultrasound imaging and inhibitory effect on the proliferation of hepatocellular carcinoma cells. Methods: The FA-PLGA/PFP-TK nanoparticles were prepared by double emulsion method and carbodiimide method. The size distribution and Zeta potential of these nanoparticles were measured using a Malvern measuring instrument, and the morphological characteristic was observed by electron microscopy. The human liver cancer SMMC-7721 cells were used to verify the targeting performance of FA-PLGA/PFP-TK nanoparticles. Low intensity focused ultrasound (LIFU) was used to detect the results of ultrasound enhanced imaging and TK gene transfecting into SMMC-7721 cells. The expression of TK protein was detected by Western blotting, and the viability of SMMC-7721 cells was evaluated by CCK-8 assay. Results: The size of nanoparticles was (207.00 ± 46.06) nm with the shape of regular sphere. The entrapment efficiency of TK gene was (34.95 ± 3.14)%. In vitro targeting experiments showed the targeting nanoparticles were gathered around SMMC-7721 cells. After LIFU irradiation, the nanoparticles could enhance the ultrasound imaging, the expression level of TK protein was increased, and the viability of SMMC-7721 cells was decreased in the FA targeting group (all P < 0.01). Conclusion: FA-PLGA/PFP-TK targeting nanoparticles are prepared successfully, which is expected to be used in ultrasound imaging-guided gene targeted therapy.