Lysosome-Targeted Gold Nanotheranostics for In Situ SERS Monitoring pH and Multimodal Imaging-Guided Phototherapy

The integration of surface-enhanced Raman spectrum (SERS) and fluorescence-photoacoustic multimodal imaging in near-infrared photothermal therapy is highly desirable for cancer theranostic. However, typically, gold nanotheranostics usually require an additional modification of fluorophores and complex design refinements. In this work, by integrating surface-modified cysteine-hydroxyl merocyanine (CyHMC) molecules onto AuNRs, a novel lysosome-targeted gold-based nanotheranostics AuNRs-CyHMC that combines the specificity of Raman spectrum, the speed of fluorescence imaging, and deep penetration of photoacoustic imaging was successfully fabricated. Interestingly, fluorescence and Raman signals in this AuNRs-CyHMC system do not interfere, but it has pH-sensitive Raman signals and self-fluorescence localization ability under different excitation wavelengths. Fluorescence co-localization experiments further confirmed the lysosome-targeting ability of AuNRs-CyHMC. Typically, the proposed nanotheranostics were capable of SERS monitoring pH changes in both phosphate-buffered saline and living cells. Meanwhile, in vitro and in vivo experiments revealed that AuNRs-CyHMC possessed excellent fluorescence-photoacoustic performance and could be used for multimodal imaging-guided photothermal therapy. Furthermore, our work implied that gold nanotheranostics can provide great potential for cancer diagnosis and treatment.