Advancing laser-activated perfluorocarbon nanodroplets as diagnostic and image-guided therapeutic agents

Abstract

Nanoparticles (NPs) have been touted as the key to revolutionizing medical diagnosis and therapy. While there have been significant advancements of NPs in the preclinical domain, NPs have struggled to gain clinical traction. Therefore, the goal of the following work was to progress towards achieving clinically-relevant image-guided NPs that can be externally “activated” to allow for enhanced image contrast and therapeutic effects. The versatility in both function and application of the studied NPs, i.e. laser-activated perfluorocarbon nanodroplets (PFCnDs), was demonstrated through studying three distinct aims. In the first aim, a novel PFCnD construct was engineered that showed improved imaging depth while maintaining attractive biocompatibility characteristics. In conjunction, an image-processing algorithm that allows for background-free imaging was developed. The second aim focused on creating a multicolored PFCnD platform for comprehensive diagnosis via multiplexed ultrasound and photoacoustic imaging. This platform helped elucidate lymphatic trafficking mechanisms of PFCnDs and unveiled important characteristics for their future use as diagnostic and therapeutic agents. The last aim demonstrated PFCnDs’ image-guided therapeutic potential by studying their ability to deliver oxygen in a controlled manner for applications in ischemic disease. Overall, the work demonstrated the versatility of laser-activated PFCnDs and showcased their clinical potential as diagnostic and image-guided therapeutic agents.