Nanosized Membrane Fusion-Triggered Three-Dimensional DNA Walker for Subtype-Specific Analysis of Breast Cancer...

Extracellular vesicles (EVs) are highly attractive in cancer diagnosis, owing to their ability to reflect the molecular characteristics of the source cells. Herein, we engineer a DNA-equipped liposome nanoprobe for developing a nanosized membrane fusion-triggered three-dimensional (3D) DNA walker for the analysis of breast cancer EVs. Specifically, liposome nanoprobes efficiently fuse with target EVs by recognizing surface-expressed epidermal growth factor receptors, thereby creating 3D tracks for the DNA walker. Subsequently, walking probes targeting human epidermal growth factor receptor-2 (HER-2) were recruited onto the fused vesicles to manipulate the walker, eventually generating considerable electrochemical signals. Results reveal a good linearity between the electrochemical output and the target EV concentration and also prove the ability of the membrane fusion-triggered DNA walker to differentiate HER-2-positive breast cancer patients and monitor the disease progression. Taken together, this work presents an effective approach for the early and subtype-specific diagnosis of breast cancer.