Solid-state emitting twisted π-conjugate as AIE-active DSE-gen: in vitro anticancer properties against FaDu and 4T1 with biocompatibility and bioimaging

Abstract

Dual-state emissive fluorogens (DSE-gens) are currently defining their importance as a transpiring tool in biological and biomedical applications. This work focuses on designing and synthesizing indole-anthracene-based solid-state emitting twisted π-conjugates using a metal-free protocol to achieve AIE-active DSE-gens, expanding their scope in biological applications. Special effort has been made to introduce proficient and photo/thermostable DSE-gens that inhibit cancer but not normal cells. Here, the lead DSE-gen initially detects cancer and normal cells by bioimaging; however, it could also confirm and distinguish cancer cells from normal cells by its abated fluorescence signal after killing cancer cells. In contrast, the fluorescence signals for a normal cell remain unscathed. Surprisingly, these molecules displayed decent anticancer properties against FaDu and 4T1 but not MCF-7 cell lines. From a series of newly designed indole-based molecules, we report one single 2,3,4-trimethoxybenzene-linked DSE-gen (the lead), exhibiting high ROS generation, less haemolysis, and less cytotoxicity than doxorubicin (DOX) for normal cells, crucial parameters for a biocompatible in vitro anticancer probe. Thus, we present a potentially applicable anticancer drug, offering a bioactive material with bioimaging efficacy and a way to detect dead cancer cells selectively. The primary mechanism behind the identified outcomes is deciphered with the support of experimental (steady-state and time-resolved fluorescence, biological assays, cellular uptake) and molecular docking studies.