{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T09:08:57Z","timestamp":1778576937331,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research, Development, and Innovation Authority","award":["12968-iau-2023-iau-R-3-1-HW-"],"award-info":[{"award-number":["12968-iau-2023-iau-R-3-1-HW-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Halloysite nanotubes (HNTs), composed of an aluminosilicate framework, are naturally abundant, biocompatible, and sustainable clay minerals with a tubular morphology and tunable surface chemistry, making them attractive platforms for targeted, multifunctional drug delivery systems. In this study, a zinc ferrite integrated halloysite nanocomposite (ZnFe2O4\/HNT) was developed via a one-pot synthesis approach for sustained release of cisplatin (Cp), aiming to reduce systemic toxicity and enhance cell-specific activity. The nanocomposites were further functionalized by integrating Cp (Cp: ZnFe2O4\/HNT ratio 0.05) and folic acid (ZnFe2O4\/HNT\/Cp: FA ratio 0.05), followed by PEGylation (0.17 \u00b5L\/mg of ZnFe2O4\/HNT\/Cp\/FA\/PEG). The structural and surface characteristics, phase, interfacial interactions (FA and Cp), and colloidal stability of nanoformulations were systematically investigated using powder X-ray diffraction analysis (XRD), Fourier transformed infrared (FT-IR) spectroscopy, zeta potential analysis, scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), high-resolution transmission electron microscopy (HRTEM), and diffuse reflectance UV\u2013visible (DRS-UV-Vis) spectroscopy. The results confirmed that ZnFe2O4 integration preserved the clay\u2019s tubular framework while inducing nanocrystallization of both ferrite and cisplatin, indicating molecular dispersion within the clay matrix. Functionalization with FA (ZnFe2O4\/HNT\/Cp\/FA) promoted amide bond linkage, modulated Cp-FA interactions, and significantly enhanced cumulative Cp release compared to the non-functionalized system ZnFe2O4\/HNT\/Cp (10.3% at 72 h vs. 34.4% at 72 h) under tumor acidic conditions (pH 6.6). PEGylation maintained the controlled release profile while improving dispersion stability. In vitro cytotoxicity studies revealed that FA-conjugated nanocomposites exhibited enhanced, time-dependent anticancer activity against HeLa cervical cancer cells, with reduced toxicity toward normal fibroblasts, indicating preferential cellular uptake via folate receptor-mediated mechanism. Overall, this work demonstrates that FA-functionalized ZnFe2O4\/HNT nanocomposite provides an effective clay-based platform for modulating Cp release and enhancing folate receptor protein-mediated targeted therapy for cervical cancer.<\/jats:p>","DOI":"10.3390\/ijms27104284","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Zinc Ferrite-Integrated Halloysite Nanotubes as a Platform for Folate-Mediated Targeted Cisplatin Delivery"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2271-8262","authenticated-orcid":false,"given":"Sarah","family":"Almofty","sequence":"first","affiliation":[{"name":"Department of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijaya","family":"Ravinayagam","sequence":"additional","affiliation":[{"name":"Deanship of Scientific Research, Imam Abdulrahman Bin Faisal University (IRMC), Dammam 31441, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatim","family":"Dafalla","sequence":"additional","affiliation":[{"name":"Core Research Facilities, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-2820","authenticated-orcid":false,"given":"B. Rabindran","family":"Jermy","sequence":"additional","affiliation":[{"name":"Department of Nanomedicine Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.micromeso.2018.10.035","article-title":"Halloysite nanotubes: Novel and eco-friendly adsorbents for high-pressure CO2 capture","volume":"277","author":"Ramadass","year":"2019","journal-title":"Microporous Mesoporous Mater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114333","DOI":"10.1016\/j.mtcomm.2025.114333","article-title":"Application of halloysite nanotubes (HNTs) in membrane technology for oil separation: A review study","volume":"50","author":"Amini","year":"2025","journal-title":"Mater. 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