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An NIR‐Responsive DNA‐Mediated Nanotetrahedron Enhances the Clearance of Senescent Cells
Author(s) -
Qu Aihua,
Wu Xiaoling,
Li Si,
Sun Maozhong,
Xu Liguang,
Kuang Hua,
Xu Chuanlai
Publication year - 2020
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202000184
Subject(s) - granzyme b , apoptosis , perforin , microbiology and biotechnology , in vivo , dna damage , fluorescence , materials science , biophysics , dna , biology , biochemistry , in vitro , cytotoxicity , physics , quantum mechanics
Senescence is a state of stable cell cycle arrest that can escape apoptosis and lead to aging and numerous age‐related diseases. In this study, an upconversion‐nanoparticle (UCNP)‐centered Au 20 –Au 30 nanoparticles tetrahedron (UAuTe) is prepared by DNA hybridization, which can selectively accelerate the clearance of senescent cells. When the beta‐2‐microglobulin antibody (anti‐B2MG) on the Au NPs recognizes senescent cells, the application of near‐infrared (NIR) light induces the disassembly of the UAuTe by breaking the boronic ester linkage. Subsequently, the Granzyme B exposed on the UCNPs induces apoptosis in senescent cells, which can then be tracked by changes in fluorescence. It is found that, as compared to single Granzyme B, the UAuTe can not only control the Granzyme B delivery by NIR‐responsivity, but also synergistically target and activate the Granzyme B in the senescent cell without the need of perforin. Moreover, this tool is applied successfully in vivo; the results demonstrate that the NIR‐responsive tetrahedron can restore renal function, tissue homeostasis, fur density, and athletic ability in a mouse model of senescence after 30 d of treatment. The NIR‐induced tetrahedron provides a practical strategy for clinical diagnosis and therapy, particularly for aging and age‐related diseases.