Biofriendly glucose-derived carbon nanodots: GLUT2-mediated cell internalization for an efficient targeted drug delivery and light-triggered cancer cell damage

Personalized medicine holds great promise for treating the underlying causes of many human diseases with high precision. Low-dimensional carbon-based materials are being designed to more closely match specific delivery efficiency for targeted cancer treatment, while enabling the benefits of increased biocompatibility, high cargo-loading capacity and excellent light-responsive properties, including photoluminescence and photothermal effects. Here, we report an unprecedented example of glucose-based carbon-nanodots (CDs-gluc) obtained via a one-pot thermal process from glucose, without using organic solvent and additional reagents. The CDs-gluc nanostructures, composed of a C-sp2 inner core and a glucose outer shell, showed a high photothermal conversion efficiency (η = 42.7 % at 532 nm), good photoluminescence quantum yield (ϕ_PL = 6 %), and low cytotoxicity. Measurements of cellular Zeta-potential demonstrated the effective interaction of CDs-gluc with the surface of cancer cells overexpressing the Glucose Transporter Type 2 (GLUT2). The effective and specific GLUT2-mediated internalization mechanism was demonstrated by inducing up- and down-regulation of the transporter expression under conditions of glucose excess and deprivation, through fluorescence correlation spectroscopy. The potential of the CDs-gluc as drug nanocarriers was demonstrated by entrapping the anticancer drug 5-fluorouracil, achieving a drug loading capacity of 4.5 ± 0.8 %. In vitro experiments confirmed the excellent light-triggered cell damage activity and remarkable cell-targeting ability of CDs-gluc driven by GLUT2 expression. The easy and green preparation, biocompatibility, effective and specific cellular uptake, photoluminescence and hyperthermia make CDs-gluc appealing candidates in the research of novel nanostructures for cancer cell targeting.