Disaccharide-polyethylenimine organic nanoparticles as non-toxic in vitro gene transporters and their anticancer potential.

Abstract

Polyethylenimines (PEIs) have been shown as efficient gene delivery vectors due to their unique properties, however, toxicity as well as non-specific interactions with the tissues/cells because of high charge density have hampered their use in clinical applications. To counter these concerns, here, we have prepared disachharide-PEI organic nanoparticles by mixing PEIs with non-reducing disaccharides, i.e. trehalose (TPONs) and sucrose (SPONs), under mild conditions. The fabricated nanoparticles were complexed with pDNA and size of these complexes was found in the range of ~130-162 nm with zeta potential ~ +8-25 mV. Further evaluation of these nanoparticles revealed that substitution of disaccharides on PEIs successfully augmented cell viability. Transfection efficiency exhibited by these complexes was significantly higher than the unmodified polymer and the standard, Lipofectamine, complexes. Fabrication of organic nanoparticles did not alter the buffering capacity considerably which was found to be instrumental during endosomal escape of the complexes. Among both the series of nanoparticles, trehalose-PEI organic nanoparticles (TPONs) exhibited greater pDNA transportation potential than sucrose-PEI organic nanoparticles (SPONs) which was also established by flow cytometric data, wherein percent cells expressing GFP was higher in case of TP/pDNA complexes as compared to SP/pDNA complexes. Interestingly, TPONs also showed promising anticancer activity on cancer cell lines i.e. Mg63, MCF-7 and HepG2. Overall, the results advocate promising potential of disaccharide-PEI organic nanoparticles as efficient gene delivery agents which can be used effectively in future gene therapy applications along with anti-cancer competence of TPONs.

• Authors: Reena Singh, Pradeep Kumar
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 112 Pg. 104918 (07 2021) ISSN: 1090-2120 [Electronic] United States
• PMID: 33932768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Disaccharides
• Polyethyleneimine
• DNA

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• DNA (genetics)
• Disaccharides (chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Gene Transfer Techniques
• Humans
• Molecular Structure
• Nanoparticles (chemistry)
• Plasmids
• Polyethyleneimine (chemistry, pharmacology)
• Structure-Activity Relationship