The Optimized Fabrication of Nanobubbles as Ultrasound Contrast Agents for Tumor Imaging.
Nanobubbles, which have the potential for ultrasonic targeted imaging and treatment in tumors, have been a research focus in recent years. With the current methods, however, the prepared uniformly sized nanobubbles either undergo post-formulation manipulation, such as centrifugation, after the mixture of microbubbles and nanobubbles, or require the addition of amphiphilic surfactants. These processes influence the nanobubble stability, possibly create material waste, and complicate the preparation process. In the present work, we directly prepared uniformly sized nanobubbles by modulating the thickness of a phospholipid film without the purification processes or the addition of amphiphilic surfactants. The fabricated nanobubbles from the optimal phospholipid film thickness exhibited optimal physical characteristics, such as uniform bubble size, good stability, and low toxicity. We also evaluated the enhanced imaging ability of the nanobubbles both in vitro and in vivo. The in vivo enhancement intensity in the tumor was stronger than that of SonoVue after injection (UCA; 2 min: 162.47 ± 8.94 dB vs. 132.11 ± 5.16 dB, P < 0.01; 5 min: 128.38.47 ± 5.06 dB vs. 68.24 ± 2.07 dB, P < 0.01). Thus, the optimal phospholipid film thickness can lead to nanobubbles that are effective for tumor imaging.
Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
Wen Bin
WB
Cai
Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
Heng Li
HL
Yang
State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
Jian
J
Zhang
Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
Ji Kai
JK
Yin
Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
Yi Lin
YL
Yang
Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
Li Jun
LJ
Yuan
Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
Li
L
Zhang
Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.
Yun You
YY
Duan
D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis*; D004339:Drug Compounding / Q000379:methods; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014463:Ultrasonography / Q000379:methods*
D003287:Contrast Media