Nucleic Acid Delivery with α-Tocopherol-Polyethyleneimine-Polyethylene Glycol Nanocarrier System

• Main Authors: Hossian AKMN, Jois SD, Jonnalagadda SC, Mattheolabakis G
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-09-01
• Series: International Journal of Nanomedicine
• Subjects: nanoparticles; gene delivery; plasmid; tocopherol; polyethyleneimine; transfection
• Online Access: https://www.dovepress.com/nucleic-acid-delivery-with-alpha-tocopherol-polyethyleneimine-polyethy-peer-reviewed-article-IJN

A K M Nawshad Hossian,1 Seetharama D Jois,1 Subash C Jonnalagadda,2 George Mattheolabakis1 1School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA, USA; 2Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ, USACorrespondence: George MattheolabakisSchool of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, 1800 Bienville Dr, Monroe, LA 71201, USATel [phone]Email [e-mail]: Nucleic acid-based therapies are a promising therapeutic tool. The major obstacle in their clinical translation is their efficient delivery to the desired tissue. We developed a novel nanosized delivery system composed of conjugates of α-tocopherol, polyethyleneimine, and polyethylene glycol (TPP) to deliver nucleic acids.Methods: We synthesized a panel of TPP molecules using different molecular weights of PEG and PEI and analyzed with various analytical approaches. The optimized version of TPP (TPP111 - the 1:1:1 molecular ratio) was self-assembled in water to produce nanostructures and then evaluated in diversified in vitro and in vivo studies.Results: Through a panel of synthesized molecules, TPP111 conjugate components self-assembled in water, forming globular shaped nanostructures of ∼ 90 nm, with high nucleic acid entrapment efficiency. The polymer had low cytotoxicity in vitro and protected nucleic acids from nucleases. Using a luciferase-expressing plasmid, TPP111-plasmid nano-complexes were rapidly up-taken by cancer cells in vitro and induced strong transfection, comparable to PEI. Colocalization of the nano-complexes and endosomes/lysosomes suggested an endosome-mediated uptake. Using a subcutaneous tumor model, intravenously injected nano-complexes preferentially accumulated to the tumor area over 24 h.Conclusion: These results indicate that we successfully synthesized the TPP111 nanocarrier system, which can deliver nucleic acids in vitro and in vivo and merits further evaluation.Keywords: nanoparticles, gene delivery, plasmid, tocopherol, polyethyleneimine, transfection