Xinjie Liu1, Jiannong Zhao1, Dajing Guo1, Zhigang Wang2, Weixiang Song1, Weijuan Chen1, Jun Zhou1. 1. Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University No. 74 Linjiang Rd, Yuzhong District, Chongqing 400010, China. 2. Institute of Ultrasound Imaging, Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University No. 74 Linjiang Rd, Yuzhong District, Chongqing 400010, China.
Abstract
BACKGROUND: Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies. However, detecting ovarian cancer at an early stage remains challenging. In this work, we aimed to synthesize a folate-receptor-targeting perfluorooctylbromide nanoparticle (FR-TPNP) as a targeted computed tomography (CT) contrast agent for the early detection of ovarian cancer. METHODS: Perfluorooctylbromide (PFOB) was encapsulated in Poly (lactic-co-glycolic acid) (PLGA) by a two-step emulsion technique to construct the nanoparticles. Folate-poly (ethylene glycol)-carboxylic acid (Fol-PEG-COOH) was introduced to modify the surface of the nanoparticles through attachment to the PLGA. The effects of different volume ratios of PFOB to PLGA on the characteristics of the FR-TPNP emulsions were compared. The size distribution and potential of the FR-TPNPs were assessed with a laser particle size analyzer system. The in vitro targeting ability of the FR-TPNPs was observed with a confocal laser scanning microscope (CLSM), and the in vivo transportation of the FR-TPNPs was evaluated with CT. RESULTS: The sizes of the FR-TPNP emulsion with different volume ratios varied from 302.67 ± 27.83 nm to 563.68 ± 47.29 nm, and the mean CT value ranged from 233 ± 20.59 HU to 587.66 ± 159.51 HU. Both the size and mean CT value increased with the volume ratio. The FR-TPNPs showed greater cell affinity and targeting efficiency to SKOV3 cells than the control group and folic acid interference group in vitro, as observed by CLSM. A significant CT enhancement of ovarian cancer xenografts in the targeted group of a nude mice model was observed 2 h post-injection; it increased to a peak at 12 h and had a duration of 48 h. The mean CT value of the tumor in the targeted group was considerably higher than those in the non-targeted and other groups 6 h post-injection. CONCLUSION: The synthesized FR-TPNP emulsion was an effective CT contrast agent with highly efficient targeting ability and a long circulation time, thus representing a potential strategy for the earlier detection of ovarian cancer.
BACKGROUND:Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies. However, detecting ovarian cancer at an early stage remains challenging. In this work, we aimed to synthesize a folate-receptor-targeting perfluorooctylbromide nanoparticle (FR-TPNP) as a targeted computed tomography (CT) contrast agent for the early detection of ovarian cancer. METHODS:Perfluorooctylbromide (PFOB) was encapsulated in Poly (lactic-co-glycolic acid) (PLGA) by a two-step emulsion technique to construct the nanoparticles. Folate-poly (ethylene glycol)-carboxylic acid (Fol-PEG-COOH) was introduced to modify the surface of the nanoparticles through attachment to the PLGA. The effects of different volume ratios of PFOB to PLGA on the characteristics of the FR-TPNP emulsions were compared. The size distribution and potential of the FR-TPNPs were assessed with a laser particle size analyzer system. The in vitro targeting ability of the FR-TPNPs was observed with a confocal laser scanning microscope (CLSM), and the in vivo transportation of the FR-TPNPs was evaluated with CT. RESULTS: The sizes of the FR-TPNP emulsion with different volume ratios varied from 302.67 ± 27.83 nm to 563.68 ± 47.29 nm, and the mean CT value ranged from 233 ± 20.59 HU to 587.66 ± 159.51 HU. Both the size and mean CT value increased with the volume ratio. The FR-TPNPs showed greater cell affinity and targeting efficiency to SKOV3 cells than the control group and folic acid interference group in vitro, as observed by CLSM. A significant CT enhancement of ovarian cancer xenografts in the targeted group of a nude mice model was observed 2 h post-injection; it increased to a peak at 12 h and had a duration of 48 h. The mean CT value of the tumor in the targeted group was considerably higher than those in the non-targeted and other groups 6 h post-injection. CONCLUSION: The synthesized FR-TPNP emulsion was an effective CT contrast agent with highly efficient targeting ability and a long circulation time, thus representing a potential strategy for the earlier detection of ovarian cancer.
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