Preparation Of Nanobubbles Modified With A Small-Molecule CXCR4 Antagonist For Targeted Drug Delivery To Tumors And Enhanced Ultrasound Molecular Imaging
Received 29 March 2019
Accepted for publication 2 September 2019
Published 26 November 2019 Volume 2019:14 Pages 9139—9157
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 4
Editor who approved publication: Dr Mian Wang
Yanli Peng,1,2,* Lianhua Zhu,1,* Luofu Wang,3 Yu Liu,1 Kejing Fang,1 Minmin Lan,1,2 Daijia Shen,1 Deng Liu,1 Zhiping Yu,3 Yanli Guo1
1Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, People’s Republic of China; 3Department of Urology, Army Featured Medicine Center, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yanli Guo
Department of Ultrasound, Southwest Hospital, Third Military Medical University (Army Medical University), No 30 Gaotanyan Street, Shapingba District, Chongqing 400038, People’s Republic of China
Tel +86 236 876 5439
Fax +86 236 876 5439
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.
Keywords: nanobubbles, ultrasound imaging, paclitaxel, AMD070, malignant tumor
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