Boosting Photoinduced Nitric Oxide Release and Photothermal Conversion through Electronic Interactions in N-Doped Carbon Nanodot Conjugates

The controlled release of nitric oxide (NO) within tumor microenvironments is an attractive strategy in anticancer therapy, as NO displays dose-dependent cytotoxic effects. Light-activated NO donors provide unique spatiotemporal precision and minimal invasiveness, making them highly suitable for biomedical applications.

Here, we describe NCDs-1, a water-soluble nanoconjugate obtained by coupling a two-step NO photodonor with blue-emitting nitrogen-doped carbon nanodots (NCDs). The resulting hybrid nanostructure (~10 nm) exhibits a new absorption band that is absent in the individual components, indicating a strong ground-state electronic interaction. Upon blue-light irradiation, NCDs-1 achieves nearly tenfold higher NO release than the free photodonor, which is a result attributed to the photoinduced electron transfer between NCDs and the NO-releasing unit. Importantly, the quenched fluorescence of NCDs is restored during the second NO release step, thus providing a real-time optical signal for monitoring the process. In addition, NCDs-1 shows remarkable photothermal conversion efficiency, supporting its potential for multimodal therapy.

To shift the light responsiveness toward more biocompatible wavelengths, we developed NCDs-2 by modifying the solvent conditions during the synthesis of NCDs while retaining citric acid and urea as precursors. This adjustment generated NCDs with absorption shifted into the green region. When conjugated with the same NO donor, NCDs-2 maintained efficient NO release upon green-light irradiation, a wavelength with improved tissue penetration and compatibility.

Preliminary in vitro experiments on cancer cell lines confirmed the therapeutic promise of both nanoconjugates. Collectively, NCDs-1 and NCDs-2 represent versatile multifunctional platforms for light-controlled NO delivery and combined photothermal therapy, with tunable optical properties adaptable to cancer diseases.