{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T11:38:30Z","timestamp":1761910710496,"version":"build-2065373602"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T00:00:00Z","timestamp":1761436800000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92249301"],"award-info":[{"award-number":["92249301"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L241026"],"award-info":[{"award-number":["L241026"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Medicine"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Sirtuin 6 (SIRT6) is a longevity\u2010associated gene with recognized therapeutic potential for vascular aging through the regulation of vascular smooth muscle cells (VSMCs) senescence. This study aims to develop a visualized nanodelivery system for a SIRT6 activator to attenuate vascular aging in a mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The expression of the vascular aging marker, osteopontin (OPN), was detected by Western blot and histological staining in the aortas of naturally aging C57BL\/6 mice. The SIRT6 activator MDL800 and the near\u2010infrared (NIR) agent indocyanine green (ICG) were encapsulated by poly(caprolactone)\u2013poly(ethylene glycol) (PCL\u2010PEG), which was modified with OPN\u2010targeting peptides, to construct OPN\u2010targeting micelles loaded with MDL800 and ICG (OPN\u2010MI). Particle size and zeta potential were assessed using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The biocompatibility and in\u00a0vitro NIR signals were evaluated in senescent VSMCs. NIR fluorescence imaging was then performed to visualize the temporal variation and biodistribution of OPN\u2010MI micelles in aging vessels. After 8\u2009weeks of intravenous injection into naturally aging mice, bioinformatics analysis, pulse wave velocity (PWV) measurement, pathological staining, and molecular biological experiments were conducted to explore the anti\u2010aging mechanism of OPN\u2010MI micelles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The expression of OPN in the aortas of naturally aging mice was significantly higher than that in control mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), confirming OPN as a target for vascular aging. The OPN\u2010MI micelles exhibited a particle size of 107.008\u2009\u00b1\u20099.572\u2009nm and a zeta potential of \u22127.293\u2009\u00b1\u20092.291\u2009mV. These micelles demonstrated excellent biocompatibility, and their strength of NIR fluorescence signals increased proportionally with the concentration of OPN\u2010MI micelles. In\u00a0vivo and ex\u00a0vivo NIR fluorescence imaging revealed that OPN\u2010MI micelles accumulated significantly in the arterial walls of aged mice compared to MI micelles (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Bioinformatics analysis and validation showed that MDL800 reduced MMP9 expression by activating SIRT6 to deacetylate H3K9ac and H3K56ac. After 8\u2009weeks of injection, the PWV of abdominal aortas in the OPN\u2010MI micelles group decreased (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.031), the number of elastin breaks in the OPN\u2010MI micelles group was reduced (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016), and the intimal\u2010medial thickness in the OPN\u2010MI micelles group was alleviated (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.048) compared to the aged group. Mechanistically, OPN\u2010MI micelles reduced MMP9 expression (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) through SIRT6 deacetylation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The visualized OPN\u2010targeted micelles encapsulating MDL800 and ICG effectively attenuate vascular aging in a naturally aging mouse model. This delivery system holds promise as a therapeutic strategy for delaying vascular aging in the future.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/agm2.70045","type":"journal-article","created":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T16:46:15Z","timestamp":1761497175000},"page":"383-397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Visualization of\n                    <scp>OPN<\/scp>\n                    \u2010Targeted Self\u2010Assembled Micelles Encapsulated With an\n                    <scp>SIRT6<\/scp>\n                    Activator and Doped Indocyanine Green for Attenuating Vascular Aging"],"prefix":"10.1002","volume":"8","author":[{"given":"Yan","family":"Fang","sequence":"first","affiliation":[{"name":"Institute of Geriatric Medicine &amp; National Clinical Research Center of Geriatric Diseases, 2nd Medical Center Chinese PLA General Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyue","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology Beijing University of Chemical Technology  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Qin","sequence":"additional","affiliation":[{"name":"Institute of Geriatric Medicine &amp; National Clinical Research Center of Geriatric Diseases, 2nd Medical Center Chinese PLA General Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengqi","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Geriatric Medicine &amp; National Clinical Research Center of Geriatric Diseases, 2nd Medical Center Chinese PLA General Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naiyuan","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Medicine Nankai University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Medicine Nankai University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyi","family":"Fang","sequence":"additional","affiliation":[{"name":"School of Medicine Nankai University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Geriatric Medicine &amp; National Clinical Research Center of Geriatric Diseases, 2nd Medical Center Chinese PLA General Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linghuan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine Nankai University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sulei","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Geriatric Medicine &amp; National Clinical Research Center of Geriatric Diseases, 2nd Medical Center Chinese PLA General Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Wan","sequence":"additional","affiliation":[{"name":"Institute of Geriatric Medicine &amp; National Clinical Research Center of Geriatric Diseases, 2nd Medical Center Chinese PLA General Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Geriatric Medicine &amp; 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