Near-Infrared Light-Responsive SERS Tags Enable Positioning and Monitoring of the Drug Release of Photothermal Nanomedicines In Vivo

Understanding the in vivo behavior of photothermal nanomedicines (PTNMs) is important for drug development and evaluation. However, it is still very challenging. Herein, two key parameters, i.e., the depth of PTNMs under biological tissue and the drug release ratio of PTNMs in vivo, can be revealed by a near-infrared (NIR) light-responsive surface-enhanced Raman scattering (SERS) strategy. The fabricated PTNMs were composed of waxberry-like gold nanoparticles, model drug curcumin, and an elaborately selected NIR light-responsive Raman reporter (3,3'-diethylthiatricarbocyanine iodide, DTTC). The response mechanism of DTTC to NIR light was investigated as photodegradation. NIR light irradiation heated the gold nanoparticles, triggered the release of a model drug, and simultaneously decreased the SERS intensity of the PTNMs. In vitro experiment results revealed that the SERS intensity decrease could well reflect the depth of PTNMs with a correlation coefficient of more than 0.99. On this basis, after in situ SERS detection, the depth of PTNMs in a tumor could be revealed with satisfactory accuracy. Moreover, the decrease in the SERS intensity of PTNMs showed a highly similar trend to the increase in the drug release, suggesting that it could be used for real-time monitoring of drug release of PTNMs. This study not only opens a new avenue for the release study of many inactive fluorescent and Raman drugs of PTNMs but also provides an effective way for reporting the depth, which greatly promotes the application of PTNMs in vivo.