Mitochondria‐Targeting Plasmonic Spiky Nanorods Increase the Elimination of Aging Cells in Vivo

Abstract

Cellular senescence is stress-induced, irreversible growth arrest, and is thought to impair tissue function. The clearance of senescent cells can delay the features of senescence.Herein, we report the development of plasmonic coreshell spikyn anorods (CSNRs) surface-modified with an antibeta-2-microglobulin (aB2MG) antibody and triphenylphosphonium (TPP), to target the mitochondria in senescent cells. aB2MG-TPP@CSNRs irradiated with near-infrared (NIR) light selectively caused mitochondrial damage and apoptosis of senescent cells with relatively low NIR light power,a nd the ability of CSNRs to activate and amplify the immune response in vitro and in vivo was discovered. The photo-induced generation of reactive oxygen species (ROS) resulted in senescentcell apoptosis and immune adjuvant effect by CSNRs accelerated the clearance of senescent cells in mice.This study opens the wayf or the use of precisely regulated plasmonic nanostructures for immune adjuvant and photo-induced apoptosis for age-related senescence.

A guide to assessing cellular senescence in vitro and in vivo

“…Despite they remain to be tested in additional models and types of senescence, some of them have served as reliable histological senescent markers in tissues [110][111][112][113][114][115]. Of note, CD9 and B2MG protein receptors have also successfully been used for the engineering of nanoparticle systems aimed at targeting senescence [73,127,128], and uPAR has recently been utilized for the development of the first senolytic CAR T cell therapy in mice [118], which highlights the potential clinical relevance of surface-centred strategies.…”

“…Interestingly, the number of mitochondria is also increased due to a reduction in their breakdown (mitophagy) upon senescence, and they grow larger showing distinct changes in their crista [69,70]. Further, changes in membrane potential have also been described, although not following a predictable pattern, with studies showing both increased and decreased potentials in senescent fibroblasts [72,73].…”

“…For example, Tri-phenyl Phosphine (TPP), a lipophilic cation moiety that targets mitochondria with increased membrane potential [74], has been re-engineered as MitoTam (combined with a modified version of Tamoxifen) and as part of polymer-based nanoparticles named PLGA to efficiently target senescent cells [75,76]. Further, a gold nanoparticle system, in which TPP was used in conjunction with the surface marker B2MG, has been reported to specifically target senescence as well [73].…”

Regulating Twisted Skeleton to Construct Organ‐Specific Perylene for Intensive Cancer Chemotherapy

“…Thanks to strong fluorescence intensity, the mitochondria‐specific ability of PDIC‐NC can well examine by co‐localization with Mito‐tracker (a mitochondrial stain). As shown in Figure 3 A, the red fluorescence of PDIC‐NC is almost completely overlapped with the green fluorescence of Mito‐tracker with high co‐localization coefficients of R A549 =0.98 and R H446 =0.89, implying the excellent mitochondria‐targeting ability of PDIC‐NC [19, 24] . Subsequently, the mitochondrial structure was observed by transmission electron microscopy (TEM).…”

“…Targeting mitochondria for pharmaceutical drugs can efficiently trigger mitochondrial dysfunction to improve the therapeutic efficiency [11–17] . In practice, some mitochondria‐targeting prodrug or nanoparticles, mainly focus on the triphenylphosphine‐modified cationic compound, have been developed to generate reactive oxygen species (ROS) in mitochondria, achieving remarkably therapeutic potency [18–24] . Based on these fundamental understandings, design idea and construction strategy of pharmaceutical drug for well achieving both organ‐ and mitochondria‐specific distribution is highly desirable to maximize the therapeutic efficiency of cancer while also minimizing side effects.…”