β‑Cyclodextrin-Coated N‑Doped Carbon Dots for Red-Light-Controlled Nitric Oxide Release and Photothermal Therapy

Photochemically controlled release of nitric oxide (NO) and photothermia are two of the most intriguing unconventional therapeutic approaches to tackle important diseases, including cancer. The development of precursors and strategies to deliver NO and induce photothermal action by exciting suitable precursors in the "therapeutic spectral window" (650-1350 nm) with the tissue-penetrating red light is highly demanding. In this contribution, N-doped carbon dots (NCD) with absorption extending up to the red region have been synthesized and covalently functionalized with β-cyclodextrins (βCyD) at their periphery. The resulting NCD-βCyD nanoscaffolds (ca. 3 nm in diameter) are dispersible in water medium and able to host a hydrophobic and otherwise blue light-activatable NO photodonor (1) within the βCyD cavity. The resulting supramolecular NCD-βCyD@1 complex is stable in a protein medium and its red light excitation simultaneously leads to (i) satisfactory fluorescence emission, (ii) NO release from 1 via a photoreductive pathway, with an upgrading of about 260 nm in the excitation wavelength, compared to 1 and (iii) efficient photothermal conversion. Due to its emissive properties, the nanoconstruct can be tracked in Caco-2 colon cancer cells, where it localizes mostly at the cytoplasmatic level. Preliminary toxicity experiments carried out with the individual components show that NCD-βCyD@1 exhibits good biocompatibility in the dark and an enhanced level of cell mortality under the exclusive control of red light against Caco-2 cell lines, due to the combined photodynamic effect of NO released from the guest precursor and the photothermal action of the NCD-βCyD core.