Tailoring of silica nanoarchitecture to optimize Cu(2−x)S based image-guided chemodynamic therapy agent

The present work introduces various synthetic and post-synthetic modes of co-doping of oleate-oleylamine-stabilized Cu (2−x) S cores with red emitting [Ru(dipy) 3 ] 2+ into amino-modified silica nanoparticles (SNs) with the aim to combine chemodynamic therapy (CDT) with cellular uptake and imaging functions. Thereto, the ROS generation by the Cu (2−x) S embedded into the SNs was manifested by the spin trap facilitated ESR technique and correlated with such parameters as size of the embedded cores, content and oxidation extent of copper ions. The parameters were varied through the different extent of an oxidative degradation of the embedded Cu (2−x) S cores by their post-treating with histidine, polyethylenimine and citrate-stabilized carbon dots (CDs). The treating by CDs was chosen as the optimal post-synthetic modification of the composite SNs due to combination of CDT with high stability to aggregation. The green or dual green-red emission of the CD-treated composite SNs visualizes their cell internalization and intracellular localization by means of fluorescence and confocal microscopy methods. Correlation of cytotoxicity data of the differently treated composite SNs with their ability to ROS generation and the intracellular localization highlight the enhanced cell internalization and nuclear confinement of the CD-treated composite SNs as the factor enhancing their cytotoxicity in greater extent than the CDT function. • Optimal architecture of silica coated Cu (2−x) S nanoparticles for high ROS generation. • Red or green emitting Cu (2−x) S nanoparticles for visualization of cellular uptake. • Surface exposure of Cu (2−x) S facilitates ROS generation. • Surface decoration by CDs for nuclear localization of Cu (2−x) S nanoparticles. • Nuclear localization of Cu (2−x) S nanoparticles enhances CDT treating of cancer cells.