Advanced biocompatible and robust platforms equipped with diverse properties are highly required in biomedical imaging applications for the early detection of atherosclerotic vascular disease and cancers. Designing nanohybrids composed of noble metals and fluorescent materials is a new way to perform multimodal imaging to overcome the limitations of single-modality counterparts. Herein, we propose the novel design of a multimodal contrast agent; namely, an enhanced nanohybrid comprising gold nanorods (GNRs) and carbon dots (CDs) with silica (SiO₂) as a bridge. The nanohybrid (GNR@SiO₂@CD) construction is based on covalent bonding between SiO₂ and the silane-functionalized CDs, which links the GNRs with the CDs to form typical core–shell units. The novel structure not only retains and even highly improves the optical properties of the GNRs and CDs, but also possesses superior imaging performance in both diffusion reflection (DR) and fluorescence lifetime imaging microscopy (FLIM) measurements compared with bare GNRs or fluorescence dyes and CDs. The superior bioimaging properties of the GNR@SiO₂@CD nanohybrids were successfully exploited for in vitro DR and FLIM measurements of macrophages within tissue-like phantoms, paving the way toward a theranostic contrast agent for atherosclerosis and cancer.

In this study, we developed a highly sensitive dual-mode imaging system using gold nanoparticles (GNPs) conjugated to various fluorophores in solid phantoms. The system consists of fluorescence-lifetime imaging microscopy (FLIM) for surface imaging, diffusion reflection (DR) for deep-tissue imaging (up to 1 cm), and metal-enhanced fluorescence (MEF). We detected quenching in the fluorescent intensity (FI) for the conjugation of both gold nanospheres (GNS) and gold nanorods (GNRs) to Fluorescein, which has an excitation peak at a wavelength shorter than the surface plasmon resonance (SPR) of both types of GNPs. Enhanced FI was detected in conjugation to Rhodamine B (RhB) and Sulforhodamine B (SRB), both with excitation peaks in the SPR regions of the GNPs. The enhanced FI was detected both in solution and in solid phantoms by the FLIM measurements. DR measurements detected the presence of GNRs within the solid phantoms by recording the dropped rates of light scattering in wavelengths corresponding to the absorption spectra of the GNRs. With the inclusion of MEF, this promising dual-mode imaging technique enables efficient and sensitive molecular and functional imaging.