Ultrasmall Glucose-Functionalized Au-Carbon Nanohybrids: Exploiting the Warburg Effect to Image Tumors by Multimodal CT/Fluorescence Imaging

Utilizing glucose as a targeting agent represents a pioneering approach in selectively directing nanoparticles towards cancer cells, capitalizing on the pronounced glucose uptake observed in tumors attributable to the Warburg effect. In this study, we have successfully adopted this targeting strategy to facilitate the specific uptake of advanced nanotools, comprising carbon nanocrystals incorporating gold seeds (AuCDs). Leveraging the advantageous optical and size-related properties of carbon nanodots in conjunction with gold-mediated X-ray attenuation capabilities, these hybrid nanomaterials have been engineered as contrast agents for a bi-modal imaging modality, exploiting the synergistic benefits of fluorescence imaging and X-ray computed tomography. Notably, for the synthesis of AuCDs, we present, for the first time, the incorporation of gold seeds within the molecular precursors of carbon nanodots during their solvothermal synthesis process, showcasing the efficacy of this synthetic pathway in yielding nanoscale carbon structures incorporating bioeliminable gold ultrasmall nanoparticles (d < 5 nm). Subsequently, we employed an azido-alkyne click chemistry reaction to functionalize the nanoparticle surface with 2-deoxy-D-glucose as a targeting moiety. The demonstrated cancer-targeting proficiency, as assessed via fluorescence imaging, renders the proposed nanosystem highly promising for a spectrum of applications in precision anticancer theranostics, encompassing both diagnostic and therapeutic endeavors.