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Herein, a thiol-functionalized ALP-responsive peptide (pY) was integrated with gold nanoparticles (Au NPs) via Au\u2013S bonds to fabricate the composite hydrogel precursor (Au-pY). Upon catalysis by tumor-overexpressed ALP, Au-pY self-assembles into Au NP-embedded composite hydrogels (Au-Gel) both intracellularly and extracellularly. Au-Gel exhibits enhanced mechanical properties compared to pure peptide hydrogels. It acts as an extracellular physical barrier and upregulates Lamin A\/C, a key protein associated with nuclear stiffness. This in turn disrupts actin cytoskeleton dynamics and suppresses the migration and invasion of HeLa cells, promoting cell apoptosis. Furthermore, Au-Gel-mediated photothermal therapy, triggered by near-infrared irradiation, potentiated the cytotoxicity against HeLa cells and facilitated cell apoptosis\/necrosis. Further in vivo investigations demonstrated that Au-Gel effectively inhibits both cervical tumor growth and lung metastasis in a HeLa cell xenograft nude mouse model. Our findings underscore the promising application of Au-Gel in cervical cancer therapy, providing novel insights and strategies into multipronged approaches to combat cervical cancer.<\/jats:p>","DOI":"10.1021\/acsami.6c14164","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:02:22Z","timestamp":1790791342000},"page":"54605-54617","source":"Crossref","is-referenced-by-count":0,"title":["Alkaline Phosphatase-Responsive Composite Hydrogels Modulating Tumor Mechanical Properties for Cervical Cancer Therapy"],"prefix":"10.1021","volume":"18","author":[{"given":"Jiaqi","family":"Wang","sequence":"first","affiliation":[{"name":"Zhengzhou University , , No. 100 Science Ave , ,","place":["Zhengzhou, PR China, 450001"]},{"name":"Henan Provincial People's Hospital , , ,","place":["Zhengzhou, PR China, 450003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingnan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , No. 100 Science Ave , ,","place":["Zhengzhou, PR China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , No. 100 Science Ave , ,","place":["Zhengzhou, PR China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Qi","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , No. 100 Science Ave , ,","place":["Zhengzhou, PR China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenguang","family":"Huang","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , No. 100 Science Ave , ,","place":["Zhengzhou, PR China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Li","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , No. 100 Science Ave , ,","place":["Zhengzhou, PR China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4128-4543","authenticated-orcid":true,"given":"Yongxing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , No. 100 Science Ave , ,","place":["Zhengzhou, PR China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3661-2338","authenticated-orcid":true,"given":"Pengchao","family":"Sun","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , No. 100 Science Ave , ,","place":["Zhengzhou, PR China, 450001"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"issue":"3","key":"2026101404072045500_cit1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2022","journal-title":"CA Cancer J. 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