An NIR-Responsive DNA-Mediated Nanotetrahedron Enhances the Clearance of Senescent Cells

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 Au₂₀ -Au₃₀ 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.