Ultrabright contrast agents with synergistic Raman enhancements for precise intraoperative imaging and photothermal ablation of orthotopic tumor models

Intraoperative imaging is critical for achieving precise cancer resection. Among available techniques, Raman spectral imaging emerges as a promising modality due to its high spatial resolution and signal stability. However, its clinical application for in vivo imaging is limited by the inherently weak Raman scattering signal. To address this challenge, we developed a novel strategy that integrates two enhancement mechanisms into a single Raman contrast agent. This contrast agent exploits the synergistic effects of an anisotropic gold nanorod and a polypyrrole-polydopamine hybrid, resulting in a substantial amplification of Raman signals. Consequently, the agent enables clear delineation of malignant tissues in both orthotopic and subcutaneous tumor models. Beyond its imaging capability, the agent also facilitates photothermal ablation, providing a long-term solution for suppressing tumor recurrence. This study systematically evaluates the imaging performance of the synthesized Raman contrast agents across different tumor models and highlights the critical role of optimizing the aspect ratio of anisotropic agents for in vivo imaging. By offering a dual-function Raman contrast agent, this research advances the potential of Raman spectral imaging for intraoperative applications and clinical translation.