Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
J Mater Chem B. 2019 Aug 7;7(31):4833-4842. doi: 10.1039/c9tb00928k.
Contrast-enhanced ultrasound (CEUS) offers the exciting prospect of retaining the ease of ultrasound imaging while enhancing imaging clarity, diagnostic specificity, and theranostic capability. To advance the capabilities of CEUS, the synthesis and understanding of new ultrasound contrast agents (UCAs) is a necessity. Many UCAs are nano- or micro-scale materials composed of a perfluorocarbon (PFC) and stabilizer that synergistically induce an ultrasound response that is both information-rich and easily differentiated from natural tissue. In this work, we probe the extent to which CEUS is modulated through variation in a PFC stabilized with fluorine-modified polydopamine nanoparticles (PDA NPs). The high level of synthetic tunability in this system allows us to study signal as a function of particle aggregation and PFC volatility in a systematic manner. Separation of aggregated and non-aggregated nanoparticles lead to a fundamentally different signal response, and for this system, PFC volatility has little effect on CEUS intensity despite a range of over 50 °C in boiling point. To further explore the imaging tunability and multimodality, Fe3+-chelation was employed to generate an enhanced photoacoustic (PA) signal in addition to the US signal. In vitro and in vivo results demonstrate that PFC-loaded PDA NPs show stronger PA signal than the non-PFC ones, indicating that the PA signal can be used for in situ differentiation between PFC-loading levels. In sum, these data evince the rich role synthetic chemistry can play in guiding new directions of development for UCAs.
超声造影（CEUS）提供了一个令人兴奋的前景，即在保持超声成像简便性的同时，提高成像清晰度、诊断特异性和治疗诊断能力。为了提高 CEUS 的能力，有必要合成和理解新的超声造影剂（UCAs）。许多 UCAs 是由全氟碳（PFC）和稳定剂组成的纳米或微米级材料，它们协同作用产生丰富的信息和易于与天然组织区分的超声响应。在这项工作中，我们研究了氟修饰的聚多巴胺纳米粒子（PDA NPs）稳定的 PFC 变化对 CEUS 的调制程度。该系统具有高度的合成可调性，使我们能够以系统的方式研究信号作为粒子聚集和 PFC 挥发性的函数。聚集和非聚集纳米粒子的分离导致了根本不同的信号响应，对于这个系统，尽管沸点范围超过 50°C，但 PFC 的挥发性对 CEUS 强度几乎没有影响。为了进一步探索成像可调性和多模态性，我们采用 Fe3+螯合来产生超声信号之外的增强光声（PA）信号。体外和体内结果表明，负载 PFC 的 PDA NPs 表现出比非 PFC 的更强的 PA 信号，表明 PA 信号可用于原位区分 PFC 负载水平。总之，这些数据表明，合成化学在指导 UCAs 的新发展方向方面可以发挥丰富的作用。
