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

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.