Activatable ultrasmall gold nanorods for "off-on" fluorescence imaging-guided photothermal therapy

Sensitive and specific fluorescence imaging-guided photothermal therapy (PTT) with high-efficiency is of essential importance and is still a challenge for nanotheranostics. To address these issues, we developed activatable ultrasmall gold nanorods (AUGNRs) to realize "off-on" switched fluorescence imaging-guided efficient PTT. Herein, the GNRs with an ultrasmall small size (∼4 nm) were set as the PTT platform due to their distinct absorption-dominant characteristics, generating an enhanced photothermal conversion efficiency. A near infrared (NIR) dye, Cy5, was conjugated to the surface of the ultrasmall GNRs for fluorescence imaging. Due to the strong localized surface plasmon resonance (LSPR), the fluorescence of Cy5 could be remarkably quenched by the GNRs and show an "off" state under normal conditions. As the AUGNRs are internalized by tumor cells, their ability of fluorescence imaging would be activated by glutathione (GSH) for the reducing action of GSH. Given the higher intracellular GSH concentration in tumor cells, a highly selective intracellular fluorescence imaging pattern was provided by the AUGNRs. As a result, the obtained AUGNRs revealed a uniformly rod-like structure with an aspect ratio of ∼4 and showed an enhanced photothermal conversion efficiency. The in vitro cellular uptake study indicated that the AUGNRs can efficiently enter the tumor cells. It has been demonstrated by in vitro Cy5 release profiles that the AUGNRs could achieve a triggered Cy5 release in response to GSH. The MTT assay and calcein AM/PI co-staining demonstrated that the cancer cells could be effectively killed when exposed to a NIR laser. Our work presents great potential for activated fluorescence imaging-guided PTT with high specificity and efficiency, as a promising method for future clinical cancer diagnostics and treatment.