A Self‐Serviced‐Track 3D DNA Walker for Ultrasensitive Detection of Tumor Exosomes by Glycoprotein Profiling

Abstract

Sensitive and accurate analysis of low‐concentration of tumor‐derived exosomes (Exos) in biofluids is essential for noninvasive cancer diagnosis but is still challenging due to the lack of high‐sensitive methods with low‐cost and easy‐operation. Herein, exploiting target Exos as a three‐dimensional (3D) track for the first time, we developed a self‐serviced‐track DNA walker (STDW) for wash‐free detection of tumor Exos using exosomal glycoprotein, which was enabled by split aptamer‐recognition‐initiated autonomous running powered by a catalytic hairpin assembly (CHA). Benefiting from high selectivity and sensitivity of the STDW assay, direct detection of tumor Exos in cell culture medium and serum could also be realized. Furthermore, this method exhibited high accuracy in clinical sample analysis, offering the potential for early cancer diagnosis and postoperative response prediction.

Advances in Designer DNA Nanorobots Enabling Programmable Functions

“…[64] Taking the exosome as 3D track and split aptamers as a recognition element, a self-serviced-track DNA walker (STDW) was designed for wash-free and highly sensitive detection of tumor exosomes by glycoprotein profiling. [65] To further explore the functionality of the continuously actuating DNA nanorobot in cell manipulation, our group recently developed an autonomous DNA nanorobot by extending the track of DNA nanorobots from fixed DNA origami to the floating receptors in the fluidic cell membrane (Figure 6d). [53] This DNA nanorobot can randomly traverse the anchor foothold of arbitrary diffused receptors mounted on fluid membranes to accumulate dimerized receptors and amplify transmembrane signals to achieve membrane surface engineering tasks.…”

“…reported a molecular recognition mechanism cellular macromolecules‐tethered DNA walking indexing (Cell‐TALKING) to probe the nano environments containing diverse chromatin modifications [64] . Taking the exosome as 3D track and split aptamers as a recognition element, a self‐serviced‐track DNA walker (STDW) was designed for wash‐free and highly sensitive detection of tumor exosomes by glycoprotein profiling [65] …”

Intelligent Dual-Lock Deoxyribonucleic Acid Automatons Boosting Precise Tumor Imaging

“…17−20 In particular, the DNA walking automatons designed by arranging DNA reaction strands on the surfaces of synthesized nanostructures have completely integrated the features of DNA and nanomaterials. 21−23 These nanomachines can enter cells efficiently and boost DNA programs through cellular endogenous stimulus, including bacteria, 24,25 proteins, 26,27 and microRNAs, 28,29 to generate signal amplifications, which exhibits great promise in tumor imaging. Despite the fact that DNA automatons adequately deal with the problem of oligonucleotides delivery at the cellular level, the nonspecific response is another predicament that confined its application in vivo.…”

Identifying the Phenotypes of Tumor-Derived Extracellular Vesicles Using Size-Coded Affinity Microbeads

“…Extracellular vesicles (EVs) are nanoscale vesicles (≈30 to 1000 nm in diameter) secreted by cells in normal and pathological conditions , that carry biological information, such as functional nucleic acids and proteins, to recipient cells. − Tumor-derived EVs (tEVs) carry both general EV transmembrane proteins (CD9, CD63, and CD81) and cancer-associated membrane proteins (EpCAM, EGFR, and PD-L1) whose expression levels are closely associated with tumor initiation, progression, and metastasis. , These tEVs have thus emerged as promising liquid biopsy biomarkers in cancer patients. , However, rapid and high-sensitivity phenotyping identification of tEVs remains challenging due to the high heterogeneity and low expression of EV surface biomarkers. Conventional detection and quantification of EV surface proteins primarily relies on enzyme-linked immunosorbent assay (ELISA) and western blot (WB) analyses, which are complex and time-consuming and have limited sensitivity and specificity.…”