Smart DNA Network Capturing and Destructing Tumor‐Derived Small Extracellular Vesicles at Tumor Sites for Localized Cancer Therapy

Abstract Tumor‐derived small extracellular vesicles (sEVs) are proven to play important roles in accelerating the progression of tumors. Destructing the sEVs at tumor sites is therefore a promising route to inhibit tumor progression. Herein, a smart DNA network‐based sEV trap (DNET) is reported, which achieved the specific capture of tumor‐derived sEVs through recognizing sEVs by polyaptamers, and the efficient destruction of sEVs via a photodynamic process at tumor sites. The DNET is constructed through the assembly of two DNA chains generated via rolling circle amplification. The DNA chains contain polyaptamers for capturing sEVs, polyvalent G‐quadruplexes for loading photodynamic reagents, and complementary segments for forming a cross‐linked network. Upon the irradiation of the laser, the captured sEVs in DNET are destructed, causing significant inhibition effects on the migration, invasion, and proliferation of glioblastoma cells. In particular, DNET achieved tumor inhibition rates of 39.70% in the zebrafish tumor model, and 73.10% in the nude mouse tumor model, respectively, demonstrating the significant efficacy of DNET in inhibiting tumor progression.