Cross-linking of S-nitrosothiolated AIEgens inside cancer cells to monitor NO release and reverse chemo-resistance

Abstract

Nitric oxide (NO)-releasing platforms have been demonstrated as promising approaches for the reversal of multidrug resistance (MDR) in cancer cells due to the suppression of P-glycoprotein (P-gp). However, the non-specific systemic release of NO and difficulty in estimating the precise NO amount in target sites hindered their translational applications. Traditional bioimaging techniques which are responsive to NO molecules cannot distinguish between exogenous and endogenous NO. Herein we introduce S-nitrosothiol-functionalized tetraphenylethene (TPE-RSNO) to specifically monitor exogenous NO release and synergistically reverse MDR. TPE-RSNO can specifically respond to NO release and visualize NO delivery with fluorescence in living cells. Moreover, the elevated reactive oxygen species (ROS) in cancer cells triggered rapid NO release to reduce P-gp and thus synergistically increase the therapeutic effect of doxorubicin (DOX).