Analysis on nanobubbles for enhanced ultrasound imaging of small-cell lung cancer in nude mice / 肿瘤研究与临床

ABSTRACT

Objective To prepare nanobubbles and analysis its application for enhanced ultrasound imaging of small-cell lung cancer (SCLC). Methods Nanobubbles were prepared using a thin-film hydration-sonication method. MTT assay was used to evaluate the cytotoxicity of the nanobubbles for SCLC H446 cell line. The contrast-enhanced ultrasound (CEUS) of xenografted SCLC tumors in 10 nude mice was performed using nanobubbles and micro-scale microbubbles, and compared with livers. The time-intensity curve (TIC) was obtained using the Gamma variate and the following parameters were calculated, including area under the curve, time to peak, arrival time, peak intensity, and half-peak time. Results Nanobubbles with spherical shape distributed homogeneously, without obvious aggregation, the mean diameters was (392.1 ±48.6) nm and average zeta potential was (-16.8 ±2.9) mV. The MTT results indicated that the nanobubbles had no obvious cytotoxicity toward H446 cell line within the concentrations used for in vivo ultrasound imaging with nanobubbles (5 μg/ml). CEUS with the nanobubbles showed significantly higher peak intensity, and half-peak time [(18.14 ±0.62) s, (141.55 ±8.21) s] in comparison with the micro-scale microbubbles [(14.82 ±0.51) s, (120.43 ±8.73) s] (P= 0.033, 0.040). There was no significant difference in time to arrival, area under the curve and time to peak (all P>0.05). Compared with livers, the nanobubbles in xenografted SCLC tumors showed significantly shorter time to peak, lower peak intensity and area under the curve, and higher half-peak time (all P 0.05). Conclusion Nanobubbles ultrasound enhanced contrast agent shows good stability and contrast-enhancement effect in vitro, and provides an experimental basis for targeting ultrasound imaging and therapeutics of SCLC.