Abstract
Objective To prepare RGD peptide modified perfluorohexane (PFH) polymer nanoparticles RGD-PFH-NPs and investigate its basic characteristics, targeting ability and combine with low-intensity focused ultrasound (LIFU) for ultrasonic imaging in vivo and vitro. Methods Targeted nanoparticles RGD-PFH-NPs were prepared by double emulsifying method and carbodiimide method. Their morphology and distribution were observed. The particle size, zeta potential and connection probability were measured. The phase-changed properties and the LIFU-induced imaging ability in contrast-enhanced ultrasound mode of RGD-PFH-NPs were investigated in vivo and vitro. The tagetability of nanoparticles to human gastric cancer cell line MGC803 and tumor-bearing nude mouse were observed through targeting group and non-targeting group. Results The prepared sample was milky white suspension liquid. The RGD-PFH-NPs were spherical uniform size, good dispersion when observed through the optical microscope and transmission electron microscopy. The particle size was (259.3±42.6)nm and the Zeta potential was (-17.6+ 5.4)mV. The connection probability of RGD peptide was 89.13%. With 70℃ water bath and LIFU stimulation RGD-PFH-NPs can remarkably change phase and show good imaging performance in both conventional ultrasound and contrast-enhanced ultrasound mode in vivo and vitro. The connection probability to MGC803 cells in targeting group (RGD-PFH-NPs ) and the non-targeting group(PFH-NPs) were 82.59% and 2.96%. The accumulation of nanoparticles in the RGD-PFH-NPs group in tumor tissues was significantly higher than that in the non-targeted PFH-NPs group(P). Conclusions The constructed nanoparticles RGD-PFH-NPs, providing contrast-enhanced ultrasonic imaging and excellent targeting ability to human gastric cancer cells MGC803 and gastric cancer tissue, is expected to become a new type of gastric cancer targeted ultrasound contrast agent. Key words: Contrast-enhanced ultrasound; Gastric cancer; Nnanoparticle; Phase change; Poly(lactic-co-glycolic acid)
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