Harnessing the gene delivery, anti-cancer and antimicrobial potential of polyethylene biguanides and their nanotized forms

• Published in: Journal of polymer research 2022-07, Vol.29 (7), Article 290
• Main Authors: Yadav, Santosh, Jha, Diksha, Gautam, Hemant K., Kumar, Pradeep
• Format: Article
• Language: English
• Subjects: Amines; Antimicrobial agents; Butanediol; Cancer; Care and treatment; Cells; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Drug resistance in microorganisms; Ethylenediaminetetraacetic acid; Gene therapy; Genetic aspects; Health aspects; Industrial Chemistry/Chemical Engineering; Low molecular weights; Lymphocytes; Methicillin; Nanoparticles; Nucleic acids; Original Paper; Polyethylene; Polyethyleneimine; Polyethylenes; Polymer Sciences; Polymers; Pseudomonas aeruginosa; T cells; Toxicity; Zeta potential
• ISSN: 1022-9760; 1572-8935
• DOI: 10.1007/s10965-022-03142-y

Here, linear polyethylenimines (lPEI, 2.5 and 25 kDa) and their nanoparticles (prepared via reaction with a crosslinker, 1,4-butanediol diglycidyl ether) have been reacted with dicyandiamide (DCDA) to form the corresponding polyethylene biguanides (PEBs) and their corresponding nanoparticles (PEB NPs) in a single step. Further, these have been examined in terms of their ability to transport nucleic acids and antibacterial activity. Biophysical characterization revealed that PEB and PEB NPs interacted efficiently with pDNA and formed stable complexes in the size range of 150–321 nm exhibiting zeta potential in the range of + 21–30 mV. Conversion of secondary amines into biguanides did not induce toxicity i.e. modified polymers and their nanoparticles remained non-toxic in HEK 293 T cells. However, these showed anti-proliferative effects in cancerous MCF-7 and A549 cells. Further, in vitro transfection assays, performed on mammalian cells (HEK 293 T and MCF-7 cells), revealed the exhibition of the highest transfection efficiency by polyethylene biguanide (2.5 kDa) nanoparticle/pDNA (PEB 2.5 NP/pDNA) complex, while it decreased in the case of PEB 25 NP/pDNA complex. Antimicrobial studies revealed that PEB 2.5 and PEB 25 polymers exhibited excellent activity against clinical isolates as well as methicillin resistant Staphylococcus aureus (MRSA) and multidrug resistant Pseudomonas aeruginosa (MDR-PA). Their corresponding nanoformulations didn’t exhibit reasonable antimicrobial activity. Altogether, the results present promising potential of the low molecular weight polyethylene biguanides as efficient carrier of nucleic acids along with the therapy for multidrug resistant infections.