Regioisomer-manipulating thio-perylenediimide nanoagents for photothermal/photodynamic theranostics
Thionated perylenediimide (PDI) can potentially generate thermal and reactive oxygen species and thus can be used as theranostic agents for photothermal/photodynamic therapy. Herein, thionated cis-/trans-isomer PDI-CS and PDI-TS were designed and prepared to investigate thionation engineering on therapeutic performance. Results revealed that photodynamic performance is less associated with the positon of sulfur atoms. By contrast, trans-isomer PDI-TS showed photothermal conversion efficiency of up to 58.4%, which is 40% higher than that of PDI-CS (~41.6%). In vitro half-maximal inhibitory concentration of ~7.78 µg mL−1 was achieved for PDI-TS, which is 1.7-fold smaller than that of PDI-CS, strongly reasserting regioisomer-modulated phototheranostic performance. Notably, the strong π–π and C···S interactions in PDI-TS nanoagents are the essential factors attributed to their excellent photothermal performance, indicating that the optimization of non-bonding interactions is an ingenious way to improve phototheranostic performance. This work provides a facile means of creating thio-perylenediimides that possess excellent antitumor property and a novel proof of concept to improve therapeutic performance through the optimization of non-bonding interactions.