Indocyanine green-loaded gold nanostars for sensitive SERS imaging and subcellular monitoring of photothermal therapy.

We have demonstrated that a typical nanothermometer was incorporated in a bovine serum albumin stabilized gold nanostar-indocyanine green (denoted as GNS-ICG-BSA) nanoprobe to realize surface-enhanced Raman scattering (SERS) imaging-based real-time sensitive monitoring of intracellular temperature in photothermal therapy (PTT), which significantly improved the spatial resolution compared to infrared thermal imaging. Herein, an exogenous thermosensitive molecule, ICG, acting as a tri-functional agent, was selected as the Raman reporter instead of direct cellular biochemical changes. The triggering of the obtained probe was unaffected by the cellular microenvironment, so it can act as a monitor of PTT in various cell types. High-resolution mass spectrometry (HRMS) was used to investigate the thermosensitive mechanism of ICG. The actively targeted GNS-ICG-BSA nanotags were used to induce SERS mapping-guided in vitro PTT of U87 glioma cells. Meanwhile, small temperature variations within a cell during PTT can be precisely monitored through the SERS fingerprint information, with a spatial resolution at the subcellular level and a sensitivity of 0.37 °C. Thus, the integrated GNS-ICG-BSA nanotags can be treated as a theranostic probe, a SERS imaging probe and an intracellular thermometer. Moreover, the good biocompatibility and the low cytotoxicity of GNS-ICG-BSA nanotags, together with their superior photothermal ablation effect on U87 glioma cells have been confirmed. This suggested that the implanted nanothermometry approach would be promising for a better understanding of the biological processes at subcellular level and provide new insights into the fabrication of a multifunctional nanoplatform. Furthermore, this study revealed that the SERS-based monitoring technique can offer great potential for theranostics as an emerging strategy.