Supramolecular self-assemblies of engineered polyethylenimines as multifunctional nanostructures for DNA transportation with excellent antimicrobial activity

• Published in: Bioorganic chemistry Vol. 106; p. 104463
• Main Authors: Singh, Reena, Jha, Diksha, Gautam, Hemant Kumar, Kumar, Pradeep
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2021
• Subjects: Antimicrobial; Cytotoxicity; Indole-3-butyric acid; Polyethylenimine; Self-assembly; Transfection; Antimicrobial; Cytotoxicity; Polyethylenimine; Self-assembly; Transfection; Indole-3-butyric acid
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.104463

[Display omitted] •Design and preparation of self-assembled cationic nanostructures for gene delivery.•LMW PEI-based nanostructures perform ~7–9 folds better than Lipofectamine.•Non-toxic supramolecular nanostructures also exhibit antimicrobial potential.•Multifunctional nanomaterials can be exploited for future gene therapy applications. In this study, indole-3-butanoic acid (IBA), a biologically and environmentally safe entity, has been grafted onto low and high molecular weight (1.8 and 25 kDa) polyethylenimines (PEI) mainly through primary amines to obtain amphiphilic indole-3-butanoyl-polyethylenimines (IBPs). Two series of IBPs (IBP1.8 and IBP25) were prepared which, on self-assembly in aqueous medium, yielded multifunctional nanomicellar structures (IBP1.8 and IBP25) capable of transporting genetic material in vitro and exhibiting other biological activities. Physicochemical characterization showed the size of IBP1.8 and IBP25 nanostructures in the range of ~332–234 nm and ~283–166 nm, respectively, with zeta potential varying from ~+29–17 mV and ~+37–25 mV. DNA release assay demonstrated higher release of plasmid DNA from IBP nanostructures as compared to native PEIs. Cytotoxicity showed a decreasing pattern with increasing degree of grafting of IBA onto PEIs making these nanostructures non-toxic. pDNA complexes of these nanostructures (both IBPs1.8 and IBPs25) displayed considerably higher transfection efficiency, however, IBP1.8/pDNA complexes performed much better (~7–9 folds) as compared to native PEI/pDNA and Lipofectamine/pDNA complexes on mammalian cells. CLSM analysis revealed that these complexes entered nucleus in sufficient amounts suggesting higher uptake and efficient internalization of the complexes. Besides, these supramolecular nanostructures not only exhibited excellent antimicrobial potential (MIC ~49–100 µg/ml) against clinical as well as resistant pathogenic strains but also found to possess antioxidant property. Overall, the projected low molecular weight PEI-based vectors could serve as more effective multifunctional nanomaterials having promising potential for future gene therapy applications with capability to provide protection against other bacterial infections.