Yanli Peng1,2, Lianhua Zhu1, Luofu Wang3, Yu Liu1, Kejing Fang1, Minmin Lan1,2, Daijia Shen1, Deng Liu1, Zhiping Yu3, Yanli Guo1. 1. Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China. 2. State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, People's Republic of China. 3. Department of Urology, Army Featured Medicine Center, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China.
Abstract
PURPOSE: To construct nanobubbles (PTX-AMD070 NBs) for targeted delivery of paclitaxel (PTX) and AMD070, examine their performance in ultrasound molecular imaging of breast cancer and cervical cancer and their therapeutic effect combined with ultrasound targeted nanobubble destruction (UTND). MATERIALS AND METHODS: PTX-AMD070 NBs were prepared via an amide reaction, and the particle size, zeta potential, encapsulation rate and drug loading efficiency were examined. Laser confocal microscopy and flow cytometry were used to analyze the targeted binding ability of PTX-AMD070 NBs to CXCR4+ MCF-7 cells and C33a cells. The effect of PTX-AMD070 NBs combined with UTND on cell proliferation inhibition and apoptosis induction was detected by CCK-8 assays and flow cytometry. The contrast-enhanced imaging features of PTX-AMD070 NBs and paclitaxel-loaded nanobubbles were compared in xenograft tumors. The penetration ability of PTX-AMD070 NBs in xenograft tissues was evaluated by immunofluorescence. The therapeutic effect of PTX-AMD070 NBs combined with UTND on xenograft tumors was assessed. RESULTS: PTX-AMD070 NBs showed a particle size of 494.3±61.2 nm, a zeta potential of -22.4±1.75 mV, an encapsulation rate with PTX of 53.73±7.87%, and a drug loading efficiency with PTX of 4.48±0.66%. PTX-AMD070 NBs displayed significantly higher targeted binding to MCF-7 cells and C33a cells than that of PTX NBs (P<0.05), and combined with UTND manifested a more pronounced effect in inhibiting cell proliferation and promoting apoptosis than other treatments. PTX-AMD070 NBs aggregated specifically in xenograft tumors in vivo, and significantly improved the image quality. Compared with other treatment groups, PTX-AMD070 NBs combined with UTND exhibited the smallest tumor volume and weight, and the highest degree of apoptosis and necrosis. CONCLUSION: PTX-AMD070 NBs improved the ultrasound imaging effect in CXCR4+ xenograft tumors and facilitated targeted therapy combined with UTND. Therefore, this study provides an effective method for the integration of ultrasound molecular imaging and targeted therapy of malignant tumors.
PURPOSE: To construct nanobubbles (PTX-AMD070 NBs) for targeted delivery of paclitaxel (PTX) and AMD070, examine their performance in ultrasound molecular imaging of breast cancer and cervical cancer and their therapeutic effect combined with ultrasound targeted nanobubble destruction (UTND). MATERIALS AND METHODS: PTX-AMD070 NBs were prepared via an amide reaction, and the particle size, zeta potential, encapsulation rate and drug loading efficiency were examined. Laser confocal microscopy and flow cytometry were used to analyze the targeted binding ability of PTX-AMD070 NBs to CXCR4+ MCF-7 cells and C33a cells. The effect of PTX-AMD070 NBs combined with UTND on cell proliferation inhibition and apoptosis induction was detected by CCK-8 assays and flow cytometry. The contrast-enhanced imaging features of PTX-AMD070 NBs and paclitaxel-loaded nanobubbles were compared in xenograft tumors. The penetration ability of PTX-AMD070 NBs in xenograft tissues was evaluated by immunofluorescence. The therapeutic effect of PTX-AMD070 NBs combined with UTND on xenograft tumors was assessed. RESULTS: PTX-AMD070 NBs showed a particle size of 494.3±61.2 nm, a zeta potential of -22.4±1.75 mV, an encapsulation rate with PTX of 53.73±7.87%, and a drug loading efficiency with PTX of 4.48±0.66%. PTX-AMD070 NBs displayed significantly higher targeted binding to MCF-7 cells and C33a cells than that of PTX NBs (P<0.05), and combined with UTND manifested a more pronounced effect in inhibiting cell proliferation and promoting apoptosis than other treatments. PTX-AMD070 NBs aggregated specifically in xenograft tumors in vivo, and significantly improved the image quality. Compared with other treatment groups, PTX-AMD070 NBs combined with UTND exhibited the smallest tumor volume and weight, and the highest degree of apoptosis and necrosis. CONCLUSION: PTX-AMD070 NBs improved the ultrasound imaging effect in CXCR4+ xenograft tumors and facilitated targeted therapy combined with UTND. Therefore, this study provides an effective method for the integration of ultrasound molecular imaging and targeted therapy of malignant tumors.
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