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Methods: In this study, we developed a locally injectable hydrogel based on synergistic dynamic covalent crosslinking (imine and boronate ester bonds), enabling instant gelation, shear thinning, and dual-pH\/ROS-responsive degradation. Two types of drug-loaded nanoparticles (NPs), coated with homotypic cell membranes, were incorporated into this hydrogel. In the acidic, reactive oxygen species (ROS)-rich tumor microenvironment (TME), the system responsively releases the antifibrotic drug SIS3 to reprogram CAFs while simultaneously delivering doxorubicin (DOX) specifically to tumor cells. Biological effects were evaluated in vitro using cell cultures and in vivo in mouse models. Results: This dynamic hydrogel-based co-delivery system effectively reprograms CAFs, reduces tumor mechanical stress, breaks the fibrotic barrier, and promotes the deep infiltration of chemotherapeutics and immune cells, thereby enhancing the efficacy of chemotherapy. Conclusions: This injectable pH\/ROS-responsive dynamic covalent hydrogel, loaded with CAF- and cancer cell-targeting NPs, remodels the TME, enhances drug and immune cell penetration, and offers a promising biomaterial-based strategy for cervical cancer treatment.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091115","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:50:44Z","timestamp":1788529844000},"page":"1115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Locally Injectable, pH\/ROS-Responsive Hydrogel Platform for Combination Therapy of Cervical Cancer with Anti-Fibrotic and Chemotherapeutic Agents"],"prefix":"10.3390","volume":"18","author":[{"given":"Qian","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6883-4632","authenticated-orcid":false,"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Biomedical Metallic Materials, Northwest Institute for Non-Ferrous Metal Research, Xi\u2019an 710014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meili","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Yu","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Biomedical Metallic Materials, Northwest Institute for Non-Ferrous Metal Research, Xi\u2019an 710014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rothenberger, N., Somasundaram, A., and Stabile, L. 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