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

Author:

Yang Sen12,Tang Jianpu12,Cheng Yu1,Liu Mingxing12,Lv Zhaoyue12,Zhang Rui12,Zhang Chunzhi3,Yao Chi1,Yang Dayong12ORCID

Affiliation:

1. Frontiers Science Center for Synthetic Biology Key Laboratory of Systems Bioengineering (MOE) School of Chemical Engineering and Technology Tianjin University Tianjin 300350 P. R. China

2. Department of Chemistry State Key Laboratory of Molecular Engineering of Polymers Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials College of Chemistry and Materials Fudan University Shanghai 200438 P. R. China

3. Department of Radiation Oncology Tianjin Hospital Tianjin University Tianjin 300211 P. R. China

Abstract

AbstractTumor‐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.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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