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A Framework Nucleic Acid Based Robotic Nanobee for Active Targeting Therapy
Author(s) -
Tian Taoran,
Xiao Dexuan,
Zhang Tao,
Li Yanjing,
Shi Sirong,
Zhong Wenyu,
Gong Ping,
Liu Zhan,
Li Qian,
Lin Yunfeng
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202007342
Subject(s) - melittin , nanotechnology , nucleic acid , dna nanotechnology , materials science , biophysics , dna , decoy , exoskeleton , cytotoxicity , membrane , biology , computer science , biochemistry , simulation , receptor , in vitro
DNA nanotechnology has provided new strategies and platforms for cargo delivery. However, DNA‐based nanostructures utilized for cargo delivery have mainly focused on static structures and passive targeting. Here, inspired by honeybee's natural reaction to hazards, a melittin loaded tetrahedron framework nucleic acid (tFNA) nanostructure, for active targeting therapy as a “nanobee” is developed. Upon exposure to target proteins on the cell membrane, the tFNA exoskeleton goes through conformation change, leading to the selective release of melittin from the exoskeleton and the consequent selective lethal effect. As a result, the active targeting of the nanobee to tumor cells is achieved. At the same concentrations of melittin, the nanobee exhibits significantly higher and more selective cytotoxicity against target cells than free melittin molecules, whereas the inactive nanobee shows neglectable lethal effect. Notably, the complete encapsulation of melittin in the tFNA exoskeleton is confirmed by the combination of experimental screening and molecular dynamic analysis, which is proposed to be the origin of the minimized off‐target effects of nanobee. This nanobee concept offers a strategy that may be extended to various dynamic stimuli‐responsive cargo delivery systems, to enhance cargo stability and decrease severe off‐target effects.