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To address these limitations, we developed a stimuli-responsive, multifunctional polymeric hydrogel by incorporating biocompatible choline-lineolate ([Cho][Lin]) ionic liquid into a sodium alginate (SA) and polyvinyl alcohol (PVA) matrix for enhanced co-delivery of doxorubicin (DOX) and zein in localized breast cancer treatment. Small-angle neutron scattering suggested the aggregation behavior of [Cho][Lin] and confirmed the solubility and stability of the drug and protein within the hydrogel. Fourier-transform infrared spectroscopy and circular dichroism demonstrated noncovalent interactions between the ionic liquid and polymers, alongside preserved protein structural integrity. Field-emission scanning electron microscopy revealed a well-defined, porous three-dimensional network with elongated fibers, while rheological analysis confirmed mechanical stability (\u03b3c = 100% strain), viscoelasticity, and shear-thinning behavior. The hydrogel exhibited self-healing, injectability, and strong adhesion, with in vitro biocompatibility assays on HaCaT cells showing &amp;gt;92% viability after 48 h. Drug and protein release studies demonstrated pH-responsive behavior, with significantly higher release under acidic conditions (89% DOX, 80% zein) than neutral pH. In vitro cytotoxicity assays on MCF-7 breast cancer cells revealed an IC50 of \u223c2 \u03bcM for the drug-loaded hydrogel. These results highlight the potential of ionic liquid-based hydrogels as a versatile and practical platform for the co-delivery of therapeutic agents, offering a targeted and efficient strategy for localized breast cancer therapy.<\/jats:p>","DOI":"10.1021\/acsabm.6c00478","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T07:56:16Z","timestamp":1785138976000},"page":"7428-7440","source":"Crossref","is-referenced-by-count":0,"title":["Ionic Liquid-Integrated Interpenetrating Polymer Hydrogel for Injectable, Self-Healing, and Stimuli-Responsive Co-Delivery of Protein and Chemotherapeutic Agents in Breast Cancer Therapy"],"prefix":"10.1021","volume":"9","author":[{"given":"Raviraj","family":"Pansuriya","sequence":"first","affiliation":[{"name":"Sardar Vallabhbhai National Institute of Technology , , , ,","place":["Surat, Gujarat, India, 395007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7529-6684","authenticated-orcid":true,"given":"Nildhara","family":"Parsana","sequence":"additional","affiliation":[{"name":"Sardar Vallabhbhai National Institute of Technology , , , ,","place":["Surat, Gujarat, India, 395007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chirag","family":"Chavda","sequence":"additional","affiliation":[{"name":"Sardar Vallabhbhai National Institute of Technology , , , ,","place":["Surat, Gujarat, India, 395007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"Assiri","sequence":"additional","affiliation":[{"name":"King Khalid University , , P.O. 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