Shirley Matthew A, Arango-Aliaga Valeria, Patel Ankit, Oeffinger Brian E, Eisenbrey John, Wheatley Margaret A
Drexel University School of Biomedical Engineering Science and Health Systems, Philadelphia, PA, USA.
Thomas Jefferson University, Philadelphia, PA, USA.
Ultrason Imaging. 2025 Jan;47(1):45-56. doi: 10.1177/01617346241279112. Epub 2024 Sep 22.
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 ( < .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% ( < .05), and the lowest max acoustic enhancement at 5 MHz (U = 19.8, C = 17.6, A = 18.9, Unloaded = 18.5 dB; < .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.
聚合物微泡作为潜在的治疗诊断剂已引起广泛关注。然而，聚合物微泡的性能可以得到极大提升，特别是在该平台的成像性能和功能多样性方面。本研究探讨将荧光碳纳米点整合到聚乳酸（PLA）微泡中。首先，通过尺寸、微泡数量、zeta电位和共振频率对制剂进行表征。然后，检测荧光性能、纳米颗粒负载量和声性能。未修饰的（U-）、羧基化的（C-）和胺化的石墨烯量子点（A-GQDs）分别在水/油/水双乳液法的有机相中以2%w/w的比例与PLA悬浮并合成。使用AccuSizer、Zetasizer、扫描电子显微镜、荧光显微镜和荧光测定法、定制的声学装置以及临床超声对新的微泡进行表征。GQD微泡的尺寸在1.4至1.9μm之间（U = 1.90，C = 1.44，A = 1.72，未负载 = 2.02μm）。U-GQD微泡表现出更高的每毫克PLA的气泡浓度（<0.05），且A-GQD微泡的zeta电位变化最大。电子显微镜显示表面光滑且呈球形，表明添加纳米颗粒没有有害影响。使用荧光显微镜的DAPI滤光片可特异性检测到A-GQD微泡，且其TRITC滤光后的荧光最高。C-GQD微泡的负载效率最高，为
