NIR-light controlled local delivery of nitric oxide based on self-targeting carbon dots

Nitric oxide (NO)-based gas therapy has received ever-increasing attention in treatment of many diseases, especially cancer. However, the selective organelle targeted delivery and controllable release of NO remains highly desirable. In this work, a sequentially targeting delivery nanoplatform has been constructed by encapsulating heat-responsive S -nitrosocysteine (the NO donor, SNC) conjugated mitochondria-targeting carbon dots (MitoCDs) and indocyanine green (ICG) within liposomes which are further modified with aptamer that can specifically bind to nucleolin overexpressed on the surface of several cancer cells. MitoCDs were prepared via one-step hydrothermal reaction using citric acid and m -diethylaminophenol as starting materials and used without any external targeting molecules. ICG molecules were employed as NIR-triggered photothermal agent followed by NO precisely controlled release in mitochondria. By combining gas and photothermal treatment, the nanocarrier produced a synergistic and superior killing effect on several cancer cell lines. And the cell growth inhibition of NCL-CSI@Lip on HEp-2 cells raised up to 72.39 %. Such an ‘all-in-one’ mitochondria-targeted NO nanocarrier may lead to new way for overcoming the problem of multidrug resistance in intracellular drug delivery.