Redox-responsive lipoic acid-modified poly ((3-amino ester) nanoparticles for enhanced gene delivery
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Tarih
2025
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Efficient 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.
Açıklama
Anahtar Kelimeler
Gene delivery, Poly ((3-amino ester) (P & Vcy;AE), Lipoic acid, Redox-responsive
Kaynak
Reactive & Functional Polymers
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
214
