Mapping Endocytic Vesicular Acidification with a pH‐Responsive DNA Nanomachine

Abstract

Mapping the endocytic vesicular acidification process is of prior importance to better understand the health and pathological processes of cells. Herein, by integrating a pH‐sensitive i‐motif and a pair of fluorescence resonance energy transfer (FRET) into a tetrahedral DNA framework (TDF), we develop a pH‐responsive DNA nanomachine, allowing for efficient sensing of pH from 7.0 to 5.5 via the pH‐triggered spatial proximity modulation of FRET. The inheriting endo‐lysosome‐targeting ability of TDF enables spatiotemporal tracking of endocytic vesicle acidification during the endosomal maturation process. Analysis of pH‐dependent FRET response at single fluorescent spot level reveals the significant difference of endocytic vesicular acidification between normal and cancer cells. The performance of pH‐responsive DNA nanomachine underlines its potential for studies on vesicle acidification‐related pathologies as a universal platform.