Tuning Proapoptotic Activity of a Phosphoric‐Acid‐Tethered Tetraphenylethene by Visible‐Light‐Triggered Isomerization and Switchable Protein Interactions for Cancer Therapy.

We herein report a phosphoric‐acid‐substituted tetraphenylethene (T‐P) capable of adapting its geometric configuration and biological activity to the microenvironment upon light irradiation for apoptosis modulation. Different from most ultraviolet‐responsive isomerization, T‐P undergoes cis‐trans isomerization under visible light irradiation, which is biocompatible and thus photo‐modulation is possible in living biosystems. By using alkaline phosphatase (ALP) and albumin as dual targets, T‐P isomers display different protein binding selectivity, cancer‐cell internalization efficiency and apoptosis‐inducing ability. The proapoptotic activity was found to be kinetically controlled by the enzymatic reaction with ALP and regulated by co‐existing albumin. Motivated by these findings, two‐way modulation of proapoptotic effect and on‐demand boosting anticancer efficacy were realized in vitro and in vivo using light and endogenous proteins as multiple non‐invasive switching stimuli. [ABSTRACT FROM AUTHOR]