新型含铁聚合物纳米气泡超声造影剂的制备及其声学特性
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摘要
目的:制备含铁的聚氰基丙烯酸丁酯(PBCA)杂化纳米气泡(UPNBs),并研究不同条件下UPNBs的性质及超声成像强度。方法:以PBCA为原料,通过乳化聚合法制备气泡并采用简单的机械搅拌法进行纯化,再用水包油的方法把氧化铁纳米粒子封装在PBCA纳米气泡中,从而得到UPNBs。用贝克曼库尔特计数器分析杂化气泡的平均直径和浓度,用电感耦合等离子体质谱仪测定铁的浓度,用超声成像仪分析不同气泡的成像对比强度。结果:经过杂化得到的纳米气泡在超声成像中有着强烈的成像对比度。此外,随着铁浓度的增加,纳米气泡的粒径仅有细微的改变,但其在超声成像中有着良好的背向散射能力。结论:这些纳米气泡有望成为超声分子成像中良好的造影剂,同时作为混合成像剂可能是核磁共振引导的超声介导的药物和基因传递的潜在载体。
Objective: To prepare iron-containing polybutyl cyanoacrylate(PBCA) hybrid nanobubbles(UPNBs) and to explore the properties and ultrasonic imaging intensity of hybrid nanobubbles under different conditions. Methods: The nanobubbles(NBs) were produced via emulsion polymerization of PBCA and were purified by a simple mechanical agitation, and the UPNBs were prepared via an oil-in-water(O/W) encapsulation of iron oxide nanoparticles in the bubble shell. The mean diameter and concentration of UPNBs were analyzed by using a Beckmann Coulter Counter. The iron concentration in different UPNBs batches was determined by inductively coupled plasma mass spectrometer(ICP-MS). Furthermore, the contrast of UPNBs in ultrasound(US) imaging was evaluated by an ultrasound scanner. Results: These polymeric NBs exhibited strong contrast in US imaging. Moreover, with the iron concentration increasing, the size of UPNBs changed slightly and they had excellent backscattering capability in US imaging. Conclusion: These nanobubbles are candidates as hybrid imaging agents for US molecular imaging, which may be potential vehicles for MRI-guided US-mediated drug and gene delivery.
Objective: To prepare iron-containing polybutyl cyanoacrylate(PBCA) hybrid nanobubbles(UPNBs) and to explore the properties and ultrasonic imaging intensity of hybrid nanobubbles under different conditions. Methods: The nanobubbles(NBs) were produced via emulsion polymerization of PBCA and were purified by a simple mechanical agitation, and the UPNBs were prepared via an oil-in-water(O/W) encapsulation of iron oxide nanoparticles in the bubble shell. The mean diameter and concentration of UPNBs were analyzed by using a Beckmann Coulter Counter. The iron concentration in different UPNBs batches was determined by inductively coupled plasma mass spectrometer(ICP-MS). Furthermore, the contrast of UPNBs in ultrasound(US) imaging was evaluated by an ultrasound scanner. Results: These polymeric NBs exhibited strong contrast in US imaging. Moreover, with the iron concentration increasing, the size of UPNBs changed slightly and they had excellent backscattering capability in US imaging. Conclusion: These nanobubbles are candidates as hybrid imaging agents for US molecular imaging, which may be potential vehicles for MRI-guided US-mediated drug and gene delivery.
引文
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[3]DAI J,ZOU S,PEI Y,et al.Polyethylenimine-grafted copolymer of poly(l-lysine)and poly(ethylene glycol)for gene delivery[J].Biomaterials,2011,32(6):1694-1705.
[4]JOLESZ F A.MRI-guided focused ultrasound surgery[J].Annu Rev Med,2009,60:417-430.
[5]CAVALLI R,BISAZZA A,TROTTA M,et al.New chitosan nanobubbles for ultrasound-mediated gene delivery:preparation and in vitro characterization[J].Int J Nanomedicine,2012,7:3309-3318.
[6]WANG Y,LI X,ZHOU Y,et al.Preparation of nanobubbles for ultrasound imaging and intracelluar drug delivery[J].Int J Pharm,2010,384(1-2):148-153.
[7]PALMOWSKI M,HUPPERT J,LADEWIG G,et al.Molecular profiling of angiogenesis with targeted ultrasound imaging:early assessment of antiangiogenic therapy effects[J].Mol Cancer Ther,2008,7(1):101-109.
[8]VAN EETEN K M P,HOUBEN H H H,VAN DER-SCHAAF J,et al.An experimental and theoretical study on the size of bubbles formed between a rotating disc and a stationary wall[J].Chem Eng Sci,2014,109(3):251-263.
[9]CAVALLI R,SOSTER M,ARGENZIANO M.Nanobubbles:a promising efficient tool for therapeutic delivery[J].Ther Deliv,2016,7(2):117-138.
[10]MARXER E E,BRüSSLER J,BECKER A,et al.Development and characterization of new nanoscaled ultrasound active lipid dispersions as contrast agents[J].Eur J Pharm Biopharm,2011,77(3):430-437.
[11]YANG H,CAI W,XU L,et al.Nanobubble-Affibody:Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor[J].Biomaterials,2015,37:279-288.
[12]MILLER D L,AVERKIOU M A,BRAYMAN A A,et al.Bioeffects considerations for diagnostic ultrasound contrast agents[J].J Ultrasound Med,2008,27(4):611-632.
[13]KAUL S.Myocardial contrast echocardiography:a 25-year retrospective[J].Circulation,2008,118(3):291-308.
[14]RAFAILIDIS V,FANG C,YUSUF G T,et al.Contrast-enhanced ultrasound(CEUS)of the abdominal vasculature[J].Abdom Radiol(NY),2018,43(4):934-947.
[15]HUANG H Y,HU S H,HUNG S Y,et al.SPIO nanoparticle-stabilized PAA-F127 thermosensitive nanobubbles with MR/US dual-modality imaging and HIFU-triggered drug release for magnetically guided in vivo tumor therapy[J].JControl Release,2013,172(1):118-127.
[16]LIU Z,LAMMERS T,EHLING J,et al.Iron oxide nanoparticle-containing microbubble composites as contrast agents for MR and ultrasound dual-modality imaging[J].Biomaterials,2011,32(26):6155-6163.
[17]SONG S,GUO H,JIANG Z,et al.Self-assembled microbubbles as contrast agents for ultrasound/magnetic resonance dual-modality imaging[J].Acta Biomater,2015,24:266-278.
[18]AO M,WANG Z,RAN H,et al.Gd-DTPA-loaded PLGAmicrobubbles as both ultrasound contrast agent and MRIcontrast agent-a feasibility research[J].J Biomed Mater Res B Appl Biomater,2010,93(2):551-556.
[19]WU H,ROGNIN N G,KRUPKA T M,et al.Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents[J].Ultrasound Med Biol,2013,39(11):2137-2146.