{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:27:57Z","timestamp":1787372877303,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018987","name":"Ministry of Research, Innovation and Digitization","doi-asserted-by":"crossref","award":["no. PNRR-III-C9\u20132022-I8\u2013291, contract no. 760081\/23.05.2023"],"award-info":[{"award-number":["no. PNRR-III-C9\u20132022-I8\u2013291, contract no. 760081\/23.05.2023"]}],"id":[{"id":"10.13039\/100018987","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Gene delivery with cationic polymers requires balancing DNA compaction, colloidal stability, and intracellular release, yet for imine-linked low-molecular-weight polyethyleneimine (PEI) vectors, quantitative relationships connecting the N\/P ratio with the full property\u2013transfection cascade remain undefined. Here, two amphiphilic non-viral vectors were prepared by linking a hydrophobic benzene\u2013siloxane core (TAS) to hyperbranched PEI (800 or 2000 Da) through reversible imine bonds and complexed with DNA across a broad N\/P range (10\u2013600). Polyplexes were characterized by atomic force microscopy (AFM), dynamic light scattering (DLS), \u03b6-potential, agarose gel electrophoresis, transfection via green fluorescent protein (GFP) imaging and luciferase assay in HeLa cells. Both vectors formed spherical nano-entities (AFM diameters ~30 nm for TAS-PEI800; ~100 nm for TAS-PEI2000). TAS-PEI2000 achieved complete DNA retardation at N\/P \u2248 30 versus N\/P \u2248 150 for TAS-PEI800, consistent with its higher charge density (\u03b6 = +37.59 vs. +18.35 mV). Transfection efficiency was superior for TAS-PEI2000 across most N\/P ratios; however, TAS-PEI2000 displayed an optimal transfection efficiency at N\/P \u2248 100 (\u03b6 \u2248 3.84 mV), beyond which efficiency declined, indicating a binding\u2013release trade-off. Cell viability remained &gt;77% across the N\/P range for TAS-PEI800, but dropped below 25% at N\/P \u2265 400 for TAS-PEI2000. A phenomenological logistic model identified characteristic transition thresholds (\u03b8 \u2248 60 for TAS-PEI800; \u03b8 \u2248 40 for TAS-PEI2000), capturing the onset of cooperative self-assembly; however, the post-optimum decline observed for TAS-PEI2000 requires additional inhibitory terms. These findings demonstrate that PEI molecular weight governs both the N\/P threshold required for efficient transfection and the width of the therapeutic window, thereby providing structure\u2013activity descriptors for the rational design of imine-linked polyplex systems.<\/jats:p>","DOI":"10.3390\/ijms27167444","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:10:20Z","timestamp":1787213420000},"page":"7444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["N\/P-Dependent DNA Complexation, Transfection, and Cytotoxicity of Imine-Linked Low-Molecular-Weight PEI Polyplexes"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5648-7896","authenticated-orcid":false,"given":"Vera-Maria","family":"Platon","sequence":"first","affiliation":[{"name":"Laboratory of Polycondensation and Thermostable Polymers, Petru Poni Institute of Macromolecular Chemistry of Romanian Academy, 700487 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8233-8862","authenticated-orcid":false,"given":"Vlad","family":"Ghizdovat","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Medical Physics, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9246-9441","authenticated-orcid":false,"given":"Iolanda","family":"Augustin","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Immunology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"Lungu","sequence":"additional","affiliation":[{"name":"Laboratory of Polycondensation and Thermostable Polymers, Petru Poni Institute of Macromolecular Chemistry of Romanian Academy, 700487 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1582-0135","authenticated-orcid":false,"given":"Constantin","family":"Volovat","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology-Radiotherapy, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana-Ioana","family":"Panaite","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology-Radiotherapy, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalina Raluca","family":"Ostafe","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology-Radiotherapy, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian Constantin","family":"Volovat","sequence":"additional","affiliation":[{"name":"Department of Radiology, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-0620","authenticated-orcid":false,"given":"Dragos-Ioan","family":"Rusu","sequence":"additional","affiliation":[{"name":"Department of Environmental Engineering, Faculty of Engineering, \u201cVasile Alecsandri\u201d University of Bacau, 600115 Bacau, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6447-0958","authenticated-orcid":false,"given":"Lacramioara","family":"Ochiuz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maricel","family":"Agop","sequence":"additional","affiliation":[{"name":"Department of Environmental Engineering, Faculty of Engineering, \u201cVasile Alecsandri\u201d University of Bacau, 600115 Bacau, Romania"},{"name":"Academy of Romanian Scientists, Ilfov, 050044 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andiana Roxana","family":"Blidari","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona Ruxandra","family":"Volovat","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology-Radiotherapy, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 University Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sainz-Ramos, M., Gallego, I., Villate-Beitia, I., Zarate, J., Maldonado, I., Puras, G., and Pedraz, J.L. (2021). How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147545"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yadegarazari, R., Lotfollahzadeh, S., Shabaninejad, Z., Pouraghajan, K., Rezaei, A., Soleymani, B., and Mohammadi, S. (2025). Recent Advances in Non-Viral Gene Delivery Systems for Hepatic Gene Therapy. Curr. Med. 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B"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7444\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:17:32Z","timestamp":1787372252000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":36,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167444"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167444","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}