Akademik Veri Yönetim Sistemi
Reactive and Functional Polymers, cilt.214, 2025 (SCI-Expanded, Scopus)
Efficient and safe delivery of genetic material into cells is a critical step in gene therapy applications. Poly (β-amino ester) (PβAE) polymers have garnered significant attention among non-viral gene delivery systems due to their biocompatibility, low toxicity, and structural versatility for modifications. However, the hydrolysis-dependent nucleic acid release mechanism of PβAE often results in uncontrolled release, thereby limiting transfection efficiency. In this study, two PβAE polymers were modified with lipoic acid to develop redox-responsive 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 PβAE and lipoic acid-modified PβAE 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 PβAE. 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 PβAE polymers hold significant potential for developing more effective gene delivery systems targeting cancer cells.