Copper phosphate micro-flowers coated with indocyanine green and iron oxide nanoparticles for in vivo localization optoacoustic tomography and magnetic actuation

Efficient drug delivery is a major challenge in modern medicine and pharmaceutical research. Micrometer-scale robots have recently been proposed as a promising venue to amplify precision of drug administration. Remotely controlled microrobots sufficiently small to navigate through microvascular networks can reach any part of the human body, yet real-time tracking is crucial for providing precise guidance and verifying successful arrival at the target. In vivo deep-tissue monitoring of individual microrobots is currently hampered by the lack of sensitivity and/or spatio-temporal resolution of commonly used clinical imaging modalities. We synthesized biocompatible and biodegradable copper phosphate micro-flowers loaded with indocyanine green and iron oxide nanoparticles to enable in vivo individual detection with localization optoacoustic tomography. We demonstrate magnetic actuation and optoacoustic tracking of these decorated micro-flowers at a per-particle level. Functional super-resolution imaging achieved via tracking intravenously injected particles provides a means of identifying microvascular targets and quantifying blood flow, while the versatile carrying capacity can be further exploited for transporting multiple types of drug formulations.