Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy.

In the ongoing search for ever-brighter surface-enhanced Raman scattering (SERS) nanoprobes, gold nanostars (AuNSs) have emerged as one of the best geometries for producing SERS in a nonaggregated state. Despite their high enhancement factor, optical extinction from plasmon-matched nanoparticles can greatly attenuate the overall SERS intensity. Herein, we report the development of a new hybrid bimetallic NS-based platform that exhibits superior resonant SERS (SERRS) properties. In this new nanoplatform, coating AuNSs with a subtotal layer of silver ([email protected]) can further increase their SERRS brightness by an order of magnitude when being interrogated by an off-resonant excitation source. Silica-encapsulated [email protected] nanoprobes were injected intradermally into a rat pelt, where SERRS was readily detected with higher signal-to-noise than nanoprobes prepared from AuNS. Moreover, these off-resonance [email protected] nanoprobes did not cause any gross photothermal damage to tissue, which was observed with the plasmon-matched AuNSs. This novel SERRS-active hybrid nanoprobe exhibits high SERRS brightness and offers promising properties for future applications in sensing and molecular imaging.