External Stimuli-Responsive Melanin-Like Nanoparticles for Photoacoustic Imaging-Guided Therapy

Photoacoustic (PA) imaging potential for biomedical applications, such as image-guide therapy, has been accelerated by exogenous contrast agent development, because of its real-time functional imaging and non-ionizing. The goal of this study was to develop melanin-like nanoparticles (MeINPs) for amplified PA imaging and pH stimuli-responsive local drug delivery. MeINPs were produced with dopamine hydrochloride and included catechol and quinone functional groups on the surface. pH sensitive MeINPs (pH-MeINPs) were synthesized by reversibly blocking free primary amines. pH-MeINPs are stable in pH > 7; however, in slightly acidic conditions (pH 5.6), pH-MeINPs are aggregated, resulting in the amplification of PA signals. Additionally, the chemotherapeutic agent, doxorubicin (DOX), was bound onto the surface of pH-MeINPs by pi-pi and hydrogen bonding. Finally, pH-MeINPs conjugated onto the surface of a 1-2-mu m sized microbubble (MB) for an externally ultrasound-controlled release of pH-MeINPs around a local tumor site. In addition, the efficient delivery and penetration of released pH-MeINPs into tumor cells can be expected because of the sonoporation of microbubbles. Results showed that under the exposure of ultrasound, DOX-pH-MeINPs were released from the microbubbles and delivered into cells more efficiently, compared to the ultrasound non-exposed control group, because of the sonoporation. The pH-MeINPs released the loaded DOX more effectively in acidic than neutral conditions. Therefore, MB-DOX-pH-MeINPs could be applied to tumor-specific PA amplification strategies; DOX-pH-MeINPs nanoparticles could be released around a tumor site with focused ultrasound, and then control DOX release locally in tumors in response to stimuli such as low pH and reactive oxygen species.