{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:06:50Z","timestamp":1789016810226,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["U1803283"],"award-info":[{"award-number":["U1803283"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82560706"],"award-info":[{"award-number":["82560706"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["U1803283"],"award-info":[{"award-number":["U1803283"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82560706"],"award-info":[{"award-number":["82560706"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Xinjiang Tianchi Academic Elite Leader Project","award":["CZ000946"],"award-info":[{"award-number":["CZ000946"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Cervical cancer cells evade chemotherapy by upregulating antioxidant defenses (e.g., glutathione (GSH)). A platform that simultaneously amplifies ROS and suppresses antioxidant defense is a low toxicity strategy. This study presents a local nanoplatform that combines chemodynamic therapy (CDT) with chemotherapy for the localized treatment of cervical cancer. Methods: Diallyl trisulfide (DATS) was loaded into the echinacoside (ECH)-copper metal\u2013phenolic networks (MPNs) nanoparticles (ECD NPs) through a one-step coordination assembly method. The nanoparticles were incorporated into a poloxamer\/HPMC thermosensitive hydrogel for vaginal delivery. The formulation was characterized for size, drug loading, sol\u2013gel transition, and pH-responsive release. Antitumor activity was evaluated in SiHa and HeLa cells via Cu2+ uptake, GSH depletion, ROS accumulation, apoptosis markers, and viability. In vivo efficacy and biosafety were assessed in an orthotopic cervical cancer model. Results: ECD NPs showed uniform size (~135 nm), high DATS loading (~27.6%). The ECD NPs-loaded hydrogel exhibited a sol\u2013gel transition at 36.7 \u00b0C. The ECD NPs-loaded hydrogel released 16.4% of DATS at pH 7.4, 32.4% at pH 4.5, 64.8% at pH 6.5, and 80.9% at pH 5.6 over 24 h. Release was minimal at vaginal pH, clearly triggered at tumor pH, and fastest at lysosomal pH, confirming pH-responsive behavior. The ECD NPs-loaded hydrogel enhanced Cu2+ uptake, depleted GSH, elevated ROS, and reduced cell viability to &lt;50% at 80 \u03bcg\/mL. In the orthotopic model, the ECD NPs hydrogel achieved a tumor inhibition rate of 87.81%, significantly outperforming free DATS (65.3%) and blank MPN (55.62%) hydrogels, with no evident systemic toxicity. Conclusions: The ECD NPs hydrogel triggers a Cu2+-driven ROS\/GSH cascade that combines copper-mediated oxidative stress with DATS-induced apoptosis for enhanced antitumor activity. Its vaginal localization, pH-responsive release, and biosafety profile support further evaluation for cervical cancer therapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091126","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:10:22Z","timestamp":1788855022000},"page":"1126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Study on Echinacoside-Copper Metal\u2013Phenolic Networks Hydrogel System Loaded with Diallyl Trisulfide for Local Treatment of Cervical Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Na","family":"Zhao","sequence":"first","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Institute for Safflower Industry Research, College of Pharmacy, Shihezi University, Shihez 832002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7580-4722","authenticated-orcid":false,"given":"Xiaoqian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Institute for Safflower Industry Research, College of Pharmacy, Shihezi University, Shihez 832002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Luo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Institute for Safflower Industry Research, College of Pharmacy, Shihezi University, Shihez 832002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Institute for Safflower Industry Research, College of Pharmacy, Shihezi University, Shihez 832002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4382-796X","authenticated-orcid":false,"given":"Yonghong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Institute for Safflower Industry Research, College of Pharmacy, Shihezi University, Shihez 832002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9845-2619","authenticated-orcid":false,"given":"Jiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Institute for Safflower Industry Research, College of Pharmacy, Shihezi University, Shihez 832002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1691-0036","authenticated-orcid":false,"given":"Le","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Institute for Safflower Industry Research, College of Pharmacy, Shihezi University, Shihez 832002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglin","family":"Hong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Institute for Safflower Industry Research, College of Pharmacy, Shihezi University, Shihez 832002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiguo","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Institute for Safflower Industry Research, College of Pharmacy, Shihezi University, Shihez 832002, China"},{"name":"College of Chemistry & Pharmacy, Northwest A&F University, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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