Poly(2-oxazoline)-Based Polyplexes as a PEG-Free Plasmid DNA Delivery Platform
Dina N. Yamaleyeva
Joint UNC-CH and NC State Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Search for more papers by this authorNaoki Makita
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Formulation Research & Development Laboratories, Technology Research & Development, Sumitomo Pharma Co., Ltd., Suita, Osaka, 564-0053 Japan
Search for more papers by this authorDuhyeong Hwang
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Department of Pharmaceutical Engineering, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, 31116 South Korea
Search for more papers by this authorMatthew J. Haney
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Search for more papers by this authorRainer Jordan
Department Chemie, Technische Universität Dresden, Zellescher Weg 19, 01069 Dresden, Germany
Search for more papers by this authorCorresponding Author
Alexander V. Kabanov
Joint UNC-CH and NC State Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
E-mail: [email protected]
Search for more papers by this authorDina N. Yamaleyeva
Joint UNC-CH and NC State Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Search for more papers by this authorNaoki Makita
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Formulation Research & Development Laboratories, Technology Research & Development, Sumitomo Pharma Co., Ltd., Suita, Osaka, 564-0053 Japan
Search for more papers by this authorDuhyeong Hwang
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Department of Pharmaceutical Engineering, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, 31116 South Korea
Search for more papers by this authorMatthew J. Haney
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Search for more papers by this authorRainer Jordan
Department Chemie, Technische Universität Dresden, Zellescher Weg 19, 01069 Dresden, Germany
Search for more papers by this authorCorresponding Author
Alexander V. Kabanov
Joint UNC-CH and NC State Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7575 USA
E-mail: [email protected]
Search for more papers by this authorAbstract
The present study expands the versatility of cationic poly(2-oxazoline) (POx) copolymers as a polyethylene glycol (PEG)-free platform for gene delivery to immune cells, such as monocytes and macrophages. Several block copolymers are developed by varying nonionic hydrophilic blocks (poly(2-methyl-2-oxazoline) (pMeOx) or poly(2-ethyl-2-oxazoline) (pEtOx), cationic blocks, and an optional hydrophobic block (poly(2-isopropyl-2-oxazoline) (iPrOx). The cationic blocks are produced by side chain modification of 2-methoxy-carboxyethyl-2-oxazoline (MestOx) block precursor with diethylenetriamine (DET) or tris(2-aminoethyl)amine (TREN). For the attachment of a targeting ligand, mannose, azide-alkyne cycloaddition click chemistry methods are employed. Of the two cationic side chains, polyplexes made with DET-containing copolymers transfect macrophages significantly better than those made with TREN-based copolymer. Likewise, nontargeted pEtOx-based diblock copolymer is more active in cell transfection than pMeOx-based copolymer. The triblock copolymer with hydrophobic block iPrOx performs poorly compared to the diblock copolymer which lacks this additional block. Surprisingly, attachment of a mannose ligand to either copolymer is inhibitory for transfection. Despite similarities in size and design, mannosylated polyplexes result in lower cell internalization compared to nonmannosylated polyplexes. Thus, PEG-free, nontargeted DET-, and pEtOx-based diblock copolymer outperforms other studied structures in the transfection of macrophages and displays transfection levels comparable to GeneJuice, a commercial nonlipid transfection reagent.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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