Development of a Polymer Ultrasound Contrast Agent Incorporating Nested Carbon Nanodots.

IF 2.5 4区 医学 Q1 ACOUSTICS Ultrasonic Imaging Pub Date : 2024-09-22 DOI:10.1177/01617346241279112
Matthew A Shirley, Valeria Arango-Aliaga, Ankit Patel, Brian E Oeffinger, John Eisenbrey, Margaret A Wheatley
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Abstract

Polymer microbubbles have garnered broad interest as potential theranostic agents. However, the capabilities of polymer MBs can be greatly enhanced, particularly regarding the imaging performance and functional versatility of the platform. This study investigates integrating fluorescent carbon nanodots within polylactic acid (PLA) microbubbles. First, the formulations are characterized by their size, microbubble counts, zeta potential, and resonance frequency. Then, the fluorescence capabilities, nanoparticle loading, and acoustic capabilities are examined. Unmodified (U-), carboxylated (C-), and aminated graphene quantum dots (A-GQDs) were separately suspended and synthesized at a 2% w/w ratio with PLA in the organic phase of the water/oil/water double emulsion process. The new microbubbles were characterized using an AccuSizer, Zetasizer, scanning electron microscopy, fluorescence microscopy and fluorimetry, a custom-built acoustic setup, and clinical ultrasound. The GQD microbubbles were sized between 1.4 and 1.9 µm (U = 1.90, C = 1.44, A = 1.72, Unloaded = 2.02 µm). The U-GQD microbubble exhibited a higher bubble concentration/mg PLA (p < .05) and the A-GQD microbubbles exhibited the greatest shift in zeta potential. Electron microscopy revealed smooth surfaces and a spherical shape, showing that the nanoparticle addition was not deleterious. The A-GQD microbubbles were specifically detectable using DAPI-filtering with fluorescence microscopy and had the highest TRITC-filtered fluorescence. The C-GQD microbubbles had the highest loading efficiency at 59.4% (p < .05), and the lowest max acoustic enhancement at 5 MHz (U = 19.8, C = 17.6, A = 18.9, Unloaded = 18.5 dB; p < .05). Additionally, all microbubbles were visible and susceptible to inertial cavitation utilizing clinical ultrasound. The A-GQDs showed promise toward improving the theranostic capabilities of the microbubble platform. They have imbued the most advantageous fluorescence capability and slightly improved backscatter enhancement while retaining all the necessary capabilities of an ultrasound contrast agent. Future studies will investigate the coloading potential of A-GQDs and drug within microbubbles.

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开发含有嵌套碳纳米点的聚合物超声造影剂
聚合物微气泡作为潜在的治疗剂已引起广泛关注。然而,聚合物微气泡的能力还可以大大提高,尤其是在成像性能和平台的功能多样性方面。本研究探讨了在聚乳酸(PLA)微气泡中整合荧光碳纳米点的问题。首先,通过尺寸、微泡数量、ZETA 电位和共振频率对配方进行表征。然后,对荧光能力、纳米粒子装载量和声学能力进行检测。在水/油/水双乳液工艺的有机相中,未改性(U-)、羧基化(C-)和胺化石墨烯量子点(A-GQDs)分别以 2% w/w 的比例与聚乳酸悬浮和合成。使用 AccuSizer、Zetasizer、扫描电子显微镜、荧光显微镜和荧光测定法、定制声学装置和临床超声波对新型微气泡进行了表征。GQD 微气泡的大小介于 1.4 和 1.9 微米之间(U = 1.90,C = 1.44,A = 1.72,无负载 = 2.02 微米)。U-GQD 微气泡表现出更高的气泡浓度/毫克聚乳酸(p p p
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来源期刊
Ultrasonic Imaging
Ultrasonic Imaging 医学-工程:生物医学
CiteScore
5.10
自引率
8.70%
发文量
15
审稿时长
>12 weeks
期刊介绍: Ultrasonic Imaging provides rapid publication for original and exceptional papers concerned with the development and application of ultrasonic-imaging technology. Ultrasonic Imaging publishes articles in the following areas: theoretical and experimental aspects of advanced methods and instrumentation for imaging
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