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

Abstract

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.

Light: A Magical Tool for Controlled Drug Delivery

“…Therefore, granzyme B exposed on the UCNPs efficiently induced senescent cell apoptosis, providing a novel strategy for clinical therapy for aging and age-related diseases ( Figure 3C). [72] biocompatible longer wavelengths under single-photon excitation or multiphoton absorption, such as the 7-amino coumarin compound modified with vinyl groups, [19c] nitrobenzyl derivative 2-(2-nitrophenyl)propyloxycarbonyl, [73] 7-diethylamino-4-thiocoumarinylmethyl protecting group, [74] modified coumarinylmethyl A) Schematic illustration of the structure of tirapazamine/upconversion nanoparticle@porphyrinic MOFs and their application to tumor treatment through a combination of NIR light-triggered photodynamic therapy and hypoxia-activated chemotherapy with immunotherapy. Reproduced with permission.…”

Engineering of chiral nanomaterials for biomimetic catalysis

“…First, exogenous additives, such as DNA or polymer, play an essential role in chiral nanostructure assembly. 38,39 Benefiting from their specific bridging effect, individual…”

Cell Senescence: A Nonnegligible Cell State under Survival Stress in Pathology of Intervertebral Disc Degeneration

“…In recent years, some drug delivery systems connected with antibodies against senescence-specific surface antigens are synthesized to solve the problem of targeted drug delivery. Qu et al used the beta-2-microglobulin antibody (anti-B2MG) to successfully construct a nanoparticle tetrahedron which could recognize and selectively clear senescent cells [ 114 ]. Amor et al screened a cell surface protein called the urokinase-type plasminogen activator receptor (uPAR) and constructed senolytic chimeric antigen receptor (CAR) T cells to eliminate target cells in multiple senescence models, which emerged as a striking senolytic strategy [ 29 ].…”