Rotaxanes as Cages to Control DNA Binding, Cytotoxicity, and Cellular Uptake of a Small Molecule**

The efficacy of many drugs can be limited by undesirable properties, such as poor aqueous solubility, low bioavailability, and off-target interactions. To combat this, various drug carriers have been investigated to enhance the pharmacological profile therapeutic agents. In this work, we demonstrate use mechanical protection cage a DNA-targeting metallodrug within photodegradable rotaxane. More specifically, report synthesis rotaxanes incorporating stoppering unit known G-quadruplex DNA binder, namely PtII -salphen complex. This compound cannot interact with when it is part mechanically interlocked assembly. second rotaxane stopper cleaved either light or an esterase, releasing system shows enhanced cell permeability cytotoxicity osteosarcoma cells compared free drug. Light activation leads dramatic increase in cytotoxicity, arising from translocation nucleus its binding DNA.