Pyrazino[2,3-g]quinoxaline-Based Nanoparticles as Near-Infrared Phototheranostic Agents for Efficient Photoacoustic-Imaging-Guided Photothermal Therapy

As the emerging phototheranostic agents, near-infrared (NIR) organic small molecules have drawn more and more attention because of the unique advantages, such as well-defined chemical structure, high purity, good reproducibility, and facile modification. However, till now, most NIR organic agents suffer from poor photothermal and physiological stabilities, which tremendously limits their clinical applications. In this work, an NIR organic small molecule (namely PQs-TPA)-based pyrazino[2,3-g]quinoxaline (PQ) by employing a donor–acceptor design strategy was synthesized. Through enclosing it with an amphiphilic biocompatible copolymer (DSPE-mPEG2000), well-distributed PQs-TPA nanoparticles (NPs) were developed, which exhibited excellent photothermal stability, reactive oxygen/nitrogen species resistances, and a high photothermal conversion efficiency up to 59.5 ± 4%. Both in vitro and in vivo experiments manifested that PQs-TPA NPs could not only serve as a high-contrast probe for photoacoustic (PA) imaging but also effectively suppress tumor growth in living mice by PA imaging-guided photothermal therapy (PTT). This study would provide an insight to design novel NIR organic small molecules and stimulate more exciting research motivations on the investigation of effective NIR organic small molecule-based agents with high performance for phototheranostic applications in living systems.