Photoresponsive Carbon Dots Decorated with Nitric Oxide Donors: Synergistic Antiparasitic Action via NO Release and Oxidative Stress.

Visceral leishmaniasis (VL), caused by Leishmania donovani (Ld), is a lethal vector-borne disease if untreated. Antimonial drugs, once effective due to their ROS-generating ability, are now largely ineffective due to rising antimony resistance in Leishmania species, accentuating the urgent need for appropriate therapies. Here, we developed nanocarbon dots decorated with a flutamide-based nitric oxide donor (NCD-NO), which, upon visible light activation, simultaneously generates singlet oxygen (1O2) and nitric oxide (NO). NO disrupts parasite metabolism, while 1O2 induces oxidative stress, together creating synergistic antiparasitic effect. Biological studies validated that dual gas release by NCD-NO mitigates the cytotoxic effects seen when NO and 1O2 are generated exclusively from nitric oxide donor (NOD) and nanocarbon dots (NCD). Intracellular parasite clearance assays revealed that NCD-NO achieves significantly higher parasite elimination while abating macrophage toxicity and selectively eradicating Leishmania amastigotes without impairing host cells.