Hybrid fibrous architectures-mediated gene transfer by pDNA nanoparticles into macrophages
Jana Ghitman,
Gratiela Gradisteanu Pircalabioru,
Calin Deleanu,
Eugeniu Vasile,
Ciprian Iliescu,
Horia Iovu
Affiliations
Jana Ghitman
Advanced Polymer Materials Group, National University of Science and Technology Politehnica Bucharest, 1-7 Gh. Polizu Street, 011061, Bucharest, Romania; Center of Excellence in Bioengineering – eBio-hub, National University of Science and Technology Politehnica Bucharest - CAMPUS, 6 Iuliu Maniu Boulevard, 061344, Bucharest, Romania
Gratiela Gradisteanu Pircalabioru
Center of Excellence in Bioengineering – eBio-hub, National University of Science and Technology Politehnica Bucharest - CAMPUS, 6 Iuliu Maniu Boulevard, 061344, Bucharest, Romania; Research Institute of the University of Bucharest (ICUB), University of Bucharest, 91-95 Splaiul Independentei, 050095, Bucharest, Romania
Calin Deleanu
“C. D. Nenitescu” Institute of Organic and Supramolecular Chemistry, 202B Splaiul Independentei, 060023 Bucharest, Romania
Eugeniu Vasile
Department of Oxide Materials Science and Engineering, National University of Science and Technology Politehnica Bucharest, 1-7 Gh. Polizu, 060042, Bucharest, Romania
Ciprian Iliescu
Center of Excellence in Bioengineering – eBio-hub, National University of Science and Technology Politehnica Bucharest - CAMPUS, 6 Iuliu Maniu Boulevard, 061344, Bucharest, Romania; Academy of Romanian Scientists, 54 Splaiul Independentei, 050094, Bucharest, Romania; National Research and Development Institute in Microtechnologies—IMT Bucharest, 126A Erou Iancu Nicolae Street, 077190, Voluntari, Romania
Horia Iovu
Advanced Polymer Materials Group, National University of Science and Technology Politehnica Bucharest, 1-7 Gh. Polizu Street, 011061, Bucharest, Romania; Center of Excellence in Bioengineering – eBio-hub, National University of Science and Technology Politehnica Bucharest - CAMPUS, 6 Iuliu Maniu Boulevard, 061344, Bucharest, Romania; Academy of Romanian Scientists, 54 Splaiul Independentei, 050094, Bucharest, Romania; Corresponding author. Advanced Polymer Materials Group, National University of Science and Technology Politehnica Bucharest, 1-7 Gh. Polizu Street, 011061, Bucharest, Romania.
Gene therapy is one of the most potential therapeutic approaches in direct and specific regulation of biological functions of macrophages at the gene level for efficient cell therapy. However, the delivery of genetic material to macrophages is extremely challenging, because of low stability, specificity and inability of therapeutic genes to efficiently enter the cells. Here, we present a method that uses the hybrid electrospun architectures based on gelatin-alginate decorated with carboxylated graphene oxide (HAG/G) as efficient substrate for loading and in vitro local and controlled delivery of plasmid DNA (pDNA) to macrophages as an alternative to systemic gene delivery carriers. Polyethyleneimine (PEI) is employed to assemble PEI/pDNA nanoparticles (Np) - used as model of carrier. The dispersion of GO-COOH sheets shifts the surface zeta potential of HAG/G to high negative value (SZP = −16.8 ± 2.21 mV) and further increases the encapsulation efficiency of PEI/pDNA Np onto hybrid HAG/G electrospun architectures to ∼ 69 % (HAG/G-Np). The in vitro biological investigations show a good metabolic activity of macrophages seeded onto HAG/G-Np (MTT assay), while gene expression experiments (fluorescent microscopy) show a 30 % increase in transient gene transfection of cells cultured in the presence of HAG/G-Np as compared to those incubated with free PEI/pDNA Np.