{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:20:57Z","timestamp":1787721657666,"version":"build-2784847793"},"reference-count":63,"publisher":"Wiley","issue":"32","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574332"],"award-info":[{"award-number":["82574332"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>ABSTRACT<\/jats:title>\n                    <jats:p>\n                      In the microenvironment of atherosclerosis (AS), excessive migration of vascular smooth muscle cells led to the formation of a thick fibrous cap. This structure acted as a physical barrier and hindered efficient drug delivery to lesional macrophages. An optimal strategy for balancing long circulation with effective penetration involved the use of size\u2010tunable nanoformulations. Leveraging highly expressed cathepsin K (CTSK) in atherosclerotic plaques, this work reported CTSK\u2010responsive, size\u2010shrinkable nanoparticles (PDE@Mn\n                      <jats:sub>3<\/jats:sub>\n                      O\n                      <jats:sub>4<\/jats:sub>\n                      \/SIM) by encapsulating trimanganese tetraoxide (Mn\n                      <jats:sub>3<\/jats:sub>\n                      O\n                      <jats:sub>4<\/jats:sub>\n                      ) and simvastatin (SIM) within CTSK\u2010cleavable block copolymers (PDE) to achieve controlled drug release and deep penetration within plaque sites. The resulting nanoparticles underwent rapid degradation and released smaller Mn\n                      <jats:sub>3<\/jats:sub>\n                      O\n                      <jats:sub>4<\/jats:sub>\n                      nanozymes, facilitating penetration into plaque macrophages. In vitro, the nanoparticles reduced reactive oxygen species levels and enhanced cholesterol efflux in macrophages. More importantly, they prolonged blood circulation and selectively accumulated in atherosclerotic plaques with high enzyme expression. They also markedly decreased macrophage infiltration and lipid deposition in plaques of AS mouse models. Collectively, these findings indicated that nanoparticles with CTSK\u2010responsive and size\u2010regulating properties achieved deep plaque penetration and precise macrophage targeting, serving as an effective anti\u2010atherosclerotic therapeutic strategy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"explicit-label\">\n                        <jats:list-item>\n                          <jats:p>Utilizing endogenously overexpressed cathepsin K in plaques as a biological stimulus could achieve precise and on\u2010demand drug release.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>By taking advantage of the size restriction imposed by fibrous caps, we designed microenvironment\u2010adaptive and size\u2010transformable nanoparticles for deep penetration.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Co\u2010delivery of Mn\n                            <jats:sub>3<\/jats:sub>\n                            O\n                            <jats:sub>4<\/jats:sub>\n                            nanozyme and SIM elicited synergistic antioxidative, antiinflammatory and lipid\u2010modulating activities to combat atherosclerosis.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/adhm.71502","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T03:55:36Z","timestamp":1785383736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A 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