Nucleic Acid Delivery with α-Tocopherol-Polyethyleneimine-Polyethylene Glycol Nanocarrier System
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, USA...
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Dove Medical Press
2020
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oai:doaj.org-article:ca0d734a526241dca0c06c4a83aeac882021-12-02T11:15:32ZNucleic Acid Delivery with α-Tocopherol-Polyethyleneimine-Polyethylene Glycol Nanocarrier System1178-2013https://doaj.org/article/ca0d734a526241dca0c06c4a83aeac882020-09-01T00:00:00Zhttps://www.dovepress.com/nucleic-acid-delivery-with-alpha-tocopherol-polyethyleneimine-polyethy-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013A 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 +1 318 342-7930Email matthaiolampakis@ulm.eduPurpose: 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, transfectionHossian AKMNJois SDJonnalagadda SCMattheolabakis GDove Medical Pressarticlenanoparticlesgene deliveryplasmidtocopherolpolyethyleneiminetransfectionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 6689-6703 (2020) |
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nanoparticles gene delivery plasmid tocopherol polyethyleneimine transfection Medicine (General) R5-920 |
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nanoparticles gene delivery plasmid tocopherol polyethyleneimine transfection Medicine (General) R5-920 Hossian AKMN Jois SD Jonnalagadda SC Mattheolabakis G Nucleic Acid Delivery with α-Tocopherol-Polyethyleneimine-Polyethylene Glycol Nanocarrier System |
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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 +1 318 342-7930Email matthaiolampakis@ulm.eduPurpose: 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 |
| format |
article |
| author |
Hossian AKMN Jois SD Jonnalagadda SC Mattheolabakis G |
| author_facet |
Hossian AKMN Jois SD Jonnalagadda SC Mattheolabakis G |
| author_sort |
Hossian AKMN |
| title |
Nucleic Acid Delivery with α-Tocopherol-Polyethyleneimine-Polyethylene Glycol Nanocarrier System |
| title_short |
Nucleic Acid Delivery with α-Tocopherol-Polyethyleneimine-Polyethylene Glycol Nanocarrier System |
| title_full |
Nucleic Acid Delivery with α-Tocopherol-Polyethyleneimine-Polyethylene Glycol Nanocarrier System |
| title_fullStr |
Nucleic Acid Delivery with α-Tocopherol-Polyethyleneimine-Polyethylene Glycol Nanocarrier System |
| title_full_unstemmed |
Nucleic Acid Delivery with α-Tocopherol-Polyethyleneimine-Polyethylene Glycol Nanocarrier System |
| title_sort |
nucleic acid delivery with α-tocopherol-polyethyleneimine-polyethylene glycol nanocarrier system |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/ca0d734a526241dca0c06c4a83aeac88 |
| work_keys_str_mv |
AT hossianakmn nucleicaciddeliverywithalphatocopherolpolyethyleneiminepolyethyleneglycolnanocarriersystem AT joissd nucleicaciddeliverywithalphatocopherolpolyethyleneiminepolyethyleneglycolnanocarriersystem AT jonnalagaddasc nucleicaciddeliverywithalphatocopherolpolyethyleneiminepolyethyleneglycolnanocarriersystem AT mattheolabakisg nucleicaciddeliverywithalphatocopherolpolyethyleneiminepolyethyleneglycolnanocarriersystem |
| _version_ |
1718396075214110720 |