{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T10:16:59Z","timestamp":1780481819437,"version":"3.54.1"},"reference-count":54,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Authority","award":["760285\/27.03.2024"],"award-info":[{"award-number":["760285\/27.03.2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Superparamagnetic iron-oxide nanoparticles (SPIONs) bearing poly(methacrylate) brushes were synthesized via surface-initiated atom-transfer radical polymerization (SI-ATRP) as magnetically responsive nanoplatforms. Three brush architectures, poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(poly(ethylene glycol) methacrylate) with six ethylene-oxide units (PPEGMA6) and ten units (PPEGMA10), were grown from a dopamine-anchored initiator and covalently loaded with methotrexate (MTX). Methods: Physicochemical characterization confirmed successful polymer grafting, tunable hydrodynamic size (185\u20131320 nm before MTX conjugation and 427\u2013694 nm after), retained superparamagnetic properties (22\u201369 emu g\u22121), and high drug payloads, with PPEGMA6 achieving 131 \u00b5g mg\u22121. MTX conjugation induced partial compaction of the polymer shell yet maintained \u03b6-potentials conducive to colloidal stability. Results: In vitro assays showed negligible toxicity toward primary human fibroblasts, whereas MTX-decorated formulations induced a pronounced concentration-dependent cytotoxic effect in MCF-7 breast cancer cells, reaching 69% loss of viability\u2014significantly higher than free MTX. Structure\u2013activity analysis attributes the superior performance of PPEGMA6-MTX to its balanced brush density, high payload, and favorable surface charge. Conclusions: These findings demonstrate that precise modulation of polymer brush architecture via SI-ATRP yields SPION-based nanocarriers that integrate MRI visibility and the potential for magnetic guidance and targeted chemotherapy. The PPEGMA6-MTX construct is highlighted as a promising platform for future preclinical investigations.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060691","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:33:14Z","timestamp":1780479194000},"page":"691","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Versatile SI-ATRP Growth of Methacrylate Brushes on Superparamagnetic Iron Oxide Nanoparticles Enables Methotrexate-Mediated Antineoplastic Activity in MCF-7 Cells"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6540-9163","authenticated-orcid":false,"given":"Razvan","family":"Ghiarasim","sequence":"first","affiliation":[{"name":"Centre of Advanced Research in Bionanoconjugates and Biopolymers, \u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Romanian Academy, Grigore Ghica Voda Alley 41 A, 700487 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1280-9515","authenticated-orcid":false,"given":"Alexandru","family":"Rotaru","sequence":"additional","affiliation":[{"name":"Centre of Advanced Research in Bionanoconjugates and Biopolymers, \u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Romanian Academy, Grigore Ghica Voda Alley 41 A, 700487 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4813-9162","authenticated-orcid":false,"given":"Cristian-Dragos","family":"Varganici","sequence":"additional","affiliation":[{"name":"Centre of Advanced Research in Bionanoconjugates and Biopolymers, \u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Romanian Academy, Grigore Ghica Voda Alley 41 A, 700487 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4021-982X","authenticated-orcid":false,"given":"Mariana","family":"Pinteala","sequence":"additional","affiliation":[{"name":"Centre of Advanced Research in Bionanoconjugates and Biopolymers, \u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Romanian Academy, Grigore Ghica Voda Alley 41 A, 700487 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6629-6460","authenticated-orcid":false,"given":"Narcisa-Laura","family":"Marangoci","sequence":"additional","affiliation":[{"name":"Centre of Advanced Research in Bionanoconjugates and Biopolymers, \u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Romanian Academy, Grigore Ghica Voda Alley 41 A, 700487 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ion","family":"Tiginyanu","sequence":"additional","affiliation":[{"name":"Centre of Advanced Research in Bionanoconjugates and Biopolymers, \u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Romanian Academy, Grigore Ghica Voda Alley 41 A, 700487 Iasi, Romania"},{"name":"National Centre for Materials Study and Testing, Technical University of Moldova, 2004 Chisinau, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5581-4624","authenticated-orcid":false,"given":"Natalia","family":"Simionescu","sequence":"additional","affiliation":[{"name":"Centre of Advanced Research in Bionanoconjugates and Biopolymers, \u201cPetru Poni\u201d Institute of Macromolecular Chemistry, Romanian Academy, Grigore Ghica Voda Alley 41 A, 700487 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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