Harnessing NIR-II luminescence in ultrasmall gold nanoparticles for enhanced biomedical applications

Ultrasmall gold nanoparticles (AuNPs, d < 3 nm) have become an outstanding type of theranostic probe because of tunable luminescence, superior pharmacokinetics, low toxicity, and rich surface chemistry. The second near-infrared (NIR-II) luminescence offers unique merits, such as deep tissue penetration, high spatial resolution, and admirable signal-noise ratio, creating many opportunities and challenges for ultrasmall AuNPs in advanced biomedical applications. Herein, this review illustrates the recent advances of ultrasmall AuNPs in understanding the NIR-II mechanisms, clearance pathways, and related biomedical applications. We firstly elucidate the present understanding of the NIR-II mechanisms of ultrasmall AuNPs, along with some effective strategies for enhancing NIR-II luminescence, namely heterometal doping and surface rigidification. Then, we discuss the impact of their structures on liver clearance and kidney clearance. Further, we highlight the major biomedical applications of these ultrasmall AuNPs in bioimaging, antibacterial, nanomedicine, and drug delivery. Finally, we offer some outlooks on the challenges and chances of ultrasmall AuNPs for later research endeavors to promote their clinical translation in the biomedical field.