The current difficulty in visualizing the true extent of malignant brain tumors during surgical resection represents one of the major reasons for the poor prognosis of brain tumor patients. Here, we evaluated the ability of a hand-held Raman scanner, guided by surface-enhanced Raman scattering (SERS) nanoparticles, to identify the microscopic tumor extent in a genetically engineered RCAS/tv-a glioblastoma mouse model. In a simulated intraoperative scenario, we tested both a static Raman imaging device and a mobile, hand-held Raman scanner. We show that SERS image-guided resection is more accurate than resection using white light visualization alone. Both methods complemented each other, and correlation with histology showed that SERS nanoparticles accurately outlined the extent of the tumors. Importantly, the hand-held Raman probe not only allowed near real-time scanning, but also detected additional microscopic foci of cancer in the resection bed that were not seen on static SERS images and would otherwise have been missed. This technology has a strong potential for clinical translation because it uses inert gold–silica SERS nanoparticles and a hand-held Raman scanner that can guide brain tumor resection in the operating room.

Complete surgical resection is the first-line treatment for most liver malignancies. This goal would be facilitated by an intraoperative imaging method that enables more precise visualization of tumor margins, and detection of otherwise invisible microscopic lesions. To this end, we synthesized silica-encapsulated surface-enhanced Raman scattering (SERS) nanoparticles (NPs) that act as a molecular imaging agent for liver malignancies. We hypothesized that, after intravenous administration, SERS NPs would avidly home to healthy liver tissue, but not to intrahepatic malignancies. We tested these SERS NPs in genetically engineered mouse models of hepatocellular carcinoma and histiocytic sarcoma. After intravenous injection, liver tumors in both models were readily identifiable with Raman imaging. In addition, Raman imaging using SERS NPs enabled detection of microscopic lesions in liver and spleen. We compared the performance of SERS NPs to fluorescence imaging using Indocyanine Green (ICG). We found that SERS NPs delineate tumors more accurately and are less susceptible to photobleaching. Given the known advantages of SERS imaging, namely high sensitivity and specific spectroscopic detection, these findings hold promise for improved resection of liver cancer.

SERS nanoprobes for in vivo biomedical applications require high quantum yield, long circulation times, and maximum colloidal stability. Traditional synthetic routes require high metal–dye affinities and are challenged by unfavorable electrostatic interactions and limited scalability. We report the synthesis of a new near-IR active poly(N-(2-hydroxypropyl) methacrylamide) (pHPMA). The integration of various SERS reporters into a biocompatible polymeric surface coating allows for controlled dye incorporation, high colloidal stability, and optimized in vivo circulation times. This technique allows the synthesis of very small (<20 nm) SERS probes, which is crucial for the design of excretable and thus highly translatable imaging agents. Depending on their size, the “schizophotonic” nanoparticles can emit both SERS and fluorescence. We demonstrate the capability of this all-in-one gold surface coating and SERS reporter for multiplexed lymph-node imaging.

Here, we report a method to specifically bind liposomal radiopharmaceuticals to a CoCrMo alloy, which can be used in arterial stents, via an irreversible inverse electron‐demand Diels–Alder reaction. Inspired by recent accomplishments in pre‐targeted imaging using tetrazine‐trans‐cyclooctene click chemistry, we synthesized 89Zr‐labeled trans‐cyclooctene‐functionalized liposomal nanoparticles, which were validated on a tetrazine‐appended polydopamine‐coated CoCrMo surface. In efforts to ultimately translate this new material to biomedical applications, we compared the ability of 89Zr‐TCO–liposomal nanoparticles (89Zr‐TCO‐LNP) to be immobilized on the tetrazine surface to the control suspensions of non‐TCO functionalized 89Zr‐liposomal nanoparticles. Ultimately, this platform technology could result in a systemic decrease of the radiotherapeutic dose deposited in non‐targeted tissues by specific removal of long‐circulating liposomal radiopharmaceuticals from the blood pool.