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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.

Tuning the ultrasonic and photoacoustic response of polydopamine-stabilized perfluorocarbon contrast agents