Redox-responsive lipoic acid-modified poly ((3-amino ester) nanoparticles for enhanced gene delivery

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dc.authorid0000-0002-9127-2380
dc.contributor.authorKaplan, Ozlem
dc.contributor.authorBal, Kevser
dc.contributor.authorSenturk, Sema
dc.contributor.authorDemir, Kamber
dc.contributor.authorGok, Mehmet Koray
dc.date.accessioned2026-01-24T12:31:17Z
dc.date.available2026-01-24T12:31:17Z
dc.date.issued2025
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractEfficient and safe delivery of genetic material into cells is a critical step in gene therapy applications. Poly ((3-amino ester) (P(3AE) polymers have garnered significant attention among non-viral gene delivery systems due to their biocompatibility, low toxicity, and structural versatility for modifications. However, the hydrolysisdependent nucleic acid release mechanism of P(3AE often results in uncontrolled release, thereby limiting transfection efficiency. In this study, two P(3AE polymers were modified with lipoic acid to develop redoxresponsive drug delivery systems, and their transfection efficiency was evaluated in cervical cancer cells (HeLa) and human embryonic kidney (HEK293T) cells. The modifications were confirmed via Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) analyses. The proton buffering capacities of P(3AE and lipoic acid-modified P(3AE within the pH range of 5.0-7.4 exhibited similar profiles. Nanoparticles were prepared from these polymers using the nanoprecipitation technique, yielding particle sizes ranging from 102.0 +/- 2.5 nm to 212.2 +/- 8.8 nm, with polydispersity index (PDI) values between 0.166 +/- 0.043 and 0.280 +/- 0.019. The zeta potential of all nanoparticles ranged from +27.3 +/- 1.1 mV to +47.4 +/- 1.7 mV. While the particle sizes remained stable over six weeks, an increasing trend in PDI values was observed. A decrease in zeta potential was recorded, attributed to the hydrolysis of P(3AE. Redox sensitivity analyses using dithiothreitol (DTT) confirmed the redox responsiveness of the nanoparticles and validated their rapid degradation under reductive conditions. In vitro studies revealed that lipoic acid modifications enhanced transfection efficiency in HeLa cells. These findings suggest that lipoic acid-modified P(3AE polymers hold significant potential for developing more effective gene delivery systems targeting cancer cells.
dc.description.sponsorshipScientific and Technological Research Council of Turkiye (TUBI TAK) under the 1002-A program [124Z384]
dc.description.sponsorshipThis study was supported by the Scientific and Technological Research Council of Turkiye (TUBI TAK) under the 1002-A program (Project No: 124Z384) .
dc.identifier.doi10.1016/j.reactfunctpolym.2025.106318
dc.identifier.issn1381-5148
dc.identifier.issn1873-166X
dc.identifier.scopus2-s2.0-105004408540
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.reactfunctpolym.2025.106318
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5785
dc.identifier.volume214
dc.identifier.wosWOS:001490603200001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofReactive & Functional Polymers
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20260121
dc.subjectGene delivery
dc.subjectPoly ((3-amino ester) (P & Vcy;AE)
dc.subjectLipoic acid
dc.subjectRedox-responsive
dc.titleRedox-responsive lipoic acid-modified poly ((3-amino ester) nanoparticles for enhanced gene delivery
dc.typeArticle

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