Nucleus delivery of doxorubicin by gadolinium-functionalized carbon dot drug delivery system for HCC imaging and therapy

To overcome the dual challenges of suboptimal therapeutic outcomes and delayed detection in hepatocellular carcinoma (HCC), a nucleus-targeting theranostic nanoplatform based on gadolinium-functionalized carbon dots (GdCDs) is presented. GdCDs were synthesized via a one-step hydrothermal method utilizing neutral red and citric acid as carbon precursors and gadolinium chloride hexahydrate as the paramagnetic source, showing good fluorescence (FL) and magnetic resonance imaging (MRI) capabilities. After modified with a nuclear localization sequence (NLS), GdCDs were loaded with doxorubicin (DOX) to yield the integrated theranostic platform: Nucleus-targeting gadolinium-functionalized carbon dot drug delivery system (NT-GdCDs-DDS) for FL/MRI dual-modality imaging and nucleus-targeting drug delivery. NT-GdCDs-DDS exhibited optimal excitation/emission wavelengths at 497/596 nm, a high longitudinal relaxivity (r₁) of 23.11 mM^-1 s^-1, and a DOX loading efficiency of 61.9%. Results of antitumor activity assays in vitro demonstrated the viability of HepG2 cells incubated with 400 μg/mL NT-GdCDs-DDS for 24 h was 8.12%, demonstrating strong antitumor activity. Furthermore, a significant tumor growth suppression in mice was observed by treated with NT-GdCDs-DDS over a 15-day period, showing superiority to free DOX. These findings establish NT-GdCDs-DDS as a potent theranostic nanoplatform for simultaneous HCC imaging and therapy.