Biofriendly Glucose-Derived Carbon Nanodots: Glut2-Mediated Cell Internalization for an Efficient Targeted Drug Delivery and Light-Triggered Cancer Cell Damage

Abstract

Personalized medicine has great potential to treat the underlying causes of many human diseases with excellent precision. Low-dimensional carbon-based materials are designed to more closely achieve specific delivery efficiency for targeted cancer treatment, while enabling the benefits of increased biocompatibility, good cargo-loading capacity and excellent light-triggered properties as photoluminescence and photothermia. Here, we report an unprecedented example of glucose-based carbon-nanodots (CDs-gluc) obtained by a one-pot thermal process from glucose without using organic solvent and reagents. The CDs-gluc nanostructures composed by a C-sp2 inner core and a glucose outer shell showed high photothermal conversion efficiency (η = 42.7 % at 532 nm), good photoluminescence yield (ϕPL= 6%) and low cytotoxicity. Measurements of cellular zeta-potential demonstrated the effective interaction of CDs-gluc  with the surface of cancer cells overexpressing GLUT2 glucose transporter. 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 deficiency, through fluorescence correlation spectroscopy. The potential of the CDs-gluc nanostructures as a drug nanocontainer was tested by entrapping of the anticancer drug 5-fluoracil with 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 the CDs-gluc driven by GLUT2 expression. The easy and green preparation, biocompatibility, effective and specific cellular internalization, photoluminescence and hyperthermia make the CDs-gluc appealing candidates in the research of novel nanostructures for cancer cell targeting.

Note:
Funding declaration: This work has been funded by European Union (NextGeneration EU), through the MUR-PNRR project SAMOTHRACE (ECS00000022).

Conflict of Interests: The authors declare no conflict of interest.

Keywords: (carbon-nanodots, cell targeting, nanomaterials, Photothermal effect, Photoluminescence, glucose-transporter)