Laser-activated perfluorocarbon nanodroplets as a tool in neurological applications

Abstract

Perfluorocarbon nanodroplets (PFCnDs) are an emerging class of nanoagents for biomedical applications. These nanoparticles are unique in their ability to phase change from liquid nanodroplet to gas microbubble when activated by electromagnetic energy. The ability of PFCnDs to phase change when triggered via an energy source has been utilized widely in the field of ultrasound (US) imaging and therapy. Upon phase change from a liquid nanodroplet to a gas microbubble by an ultrasound pulse, PFCnDs can provide US imaging contrast and can act as delivery vehicles for various types of cargo. PFCnDs used in US therapy have also been employed to act as mechanical agents, creating pores in cell membranes and interrogating biological barriers. Recently, laser-activated PFCnDs have been investigated. This subset of PFCnDs are vaporized optically and require a highly absorbing optical trigger contained within the droplet to induce phase change. The dual ultrasound and photoacoustic (PA) imaging contrast inherently provided by laser-activated PFCnDs is used in a variety of imaging techniques, from super-resolution imaging to molecular and functional imaging. In addition, applications of laser-activated PFCnDs as a therapeutic agent are currently being explored. Due to their versatile nature and dual imaging contrast, laser-activated PFCnDs present themselves as a promising biomedical imaging and therapy tool. In particular, laser-activated PFCnDs can be used to address certain challenges involved in treating diseases and disorders of the central nervous system (CNS). One major roadblock to successful treatment of neurological diseases is the blood brain barrier (BBB), a semipermeable barrier that often prevents extravasation of therapeutics or imaging contrast from the vasculature into brain tissue. To address this challenge, laser-activated PFCnDs can be developed as mechanical agents, to open the BBB noninvasively. Furthermore, laser-activated PFCnD US/PA imaging contrast can also be utilized for in vivo neuroimaging techniques. Therefore, the goal of this work is to develop laser-activated PFCnDs as a tool in neurological applications, ranging from opening biological barriers to providing US/PA imaging contrast within the CNS. Specifically, PFCnDs are synthesized to open the BBB and are evaluated qualitatively, histologically, and through US/PA imaging techniques. In addition, laser parameters used to trigger PFCnD vaporization are optimized to ensure safe and effective laser-activated PFCnD induced BBB opening. Laser-activated PFCnDs are also evaluated as a US/PA neuroimaging contrast agent through in vitro and in vivo studies. Overall, the results of these studies showcase the far-reaching capabilities of laser-activated PFCnDs in neurological applications.