Gold nanorods combine photoacoustic and Raman imaging for detection and treatment of ovarian cancer

Gold nanorods (GNRs) were synthesized with surfactant templating and coated with IR792 to produce surface-enhanced Raman signal (SERS). Subcutaneous and orthotopic tumor models were created in nude mice using the OV2008 cell line, and a Nexus128 scanner from Endra LifeSciences was used to collect the photoacoustic data. We used GNRs with resonance at 756 nm, and the Raman signal was 10-fold larger than 60 nm gold core/silica shell nanoparticles. This signal was stable for over 24 hours in 50% serum. The batch-to-batch reproducibility was 15.5% and 3.6% in the SERS and photoacoustic modalities for n=4 batches. Animals were injected with 200 μL of 2.5, 5.4, and 16.8 nM GNRs. Relative to baseline photoacoustic signal, these concentrations increased tumor signal 1.3-, 1.6-, and 2.5-fold, respectively. The maximum signal increase occurred within 2 hours of injection persisted for at least 24 hours and was significant at p<0.05 for at least 3 animals. Assaying for gold in the tumors validated signal—we found a strong correlation (R2>0.90) between tumor gold concentration and photoacoustic signal. By 24 hours, free GNRs had been sequestered to the liver and spleen with 2%ID/g immobilized in the tumor. The same GNRs produced SERS signal, and Raman maps were created with least squares analysis. We used the Raman signal to identify tumor margins and also to monitor resection and ensure complete removal of tumor tissue. Thus, the GNRs allow pre-surgical photoacoustic visualization for tumor staging and intra-operative Raman imaging to guide resection. Future work will study GNRs targeted to cell surface proteins to increase tumor accumulation.