Molecular Logic Gate for Sensing pH/Peroxynitrite with Potential Applications in Cisplatin Treatment

Cisplatin is a common chemotherapy drug for multiple solid tumors; however, due to the nitrification of peroxynitrite (ONOO-), a series of side effects seriously affect its dose and efficacy. Considering that the reactivity of ONOO- is significantly affected by pH in vitro, revealing their roles in living cells contributes to understanding the side-effect process induced by cisplatin. Herein, we present a near-infrared fluorescent logic gate for sensing pH/ONOO-, which can accurately discriminate four scenarios (no analyte, analyte H+ alone, analyte ONOO- alone, and H+ + ONOO-) and which one comes first. With this probe, the significant roles of pH and ONOO- in cisplatin treatment are disclosed, in which the cell account shows a dramatic reduction accompanied by decreased pH and upregulated ONOO- levels. By artificially recovering the pH, the ONOO- content and cell account can maintain a stable state, possibly due to the protection from acidification and nitration. This work provides an ideal pH/ONOO- logical sensor for revealing their potential roles under cisplatin, which is expected to proffer new insights into more related diseases and drug research.