Development of adjustable chiral graphene nanosheet for light-activated cytotoxic therapy

Chiral graphene nanosheets are attractive for biomedical applications; however, their fixed stereochemistry limits their precise directionality in cells. This work develops adjustable chiral graphene nanosheets (ACGNs) whose handedness and bioactivity can be switched with light, enabling light-activated cytotoxic therapy. Nanosheets were functionalized with photoisomerizable azobenzene. Ultraviolet light induces a trans to cis isomerization that twists the lattice into a distinct chiral state; visible light then returns the cis to trans isomerization, relaxing the framework into an alternative configuration. Circular dichroism and anisotropy (g-factor) measurements show clean, reversible sign inversions with minimal absorbance drift, confirming concentration-independent, fatigue-resistant switching and stable surface conjugation.The biological consequence of this stereochemical control is an isomer-dependent cytotoxic response. In vitro, the trans state consistently shows relatively higher toxicity than the cis state across the tested concentration range, whereas the graphene nanosheet racemic mixture remains medium biocompatible. Because light toggles trans↔cis on demand, ACGNs operate as a photopharmacology “on/off” switch: materials can be delivered in the low-toxicity cis form for circulation and uptake,Overall, these findings provide a robust platform in which chiroptical state and therapeutic efficacy are strongly connected and light addressable. The ability to adjust bioactivity without altering composition enables targeted cytotoxic therapy while minimizing systemic exposure. This thesis establishes the experimental and conceptual foundation for changeable chiral graphene nanosheets as light-controlled cytotoxics, paving the way for targeted, image-guided treatments and combinatorial regimens that leverage reversible stereochemistry in biological systems.