Low molecular weight polyethylenimine-grafted soybean protein gene carriers with low cytotoxicity and greatly improved transfection in vitro

Abstract

A series of gene carriers (SP-PEI) have been synthesized by acylation reaction between soybean protein and branched polyethylenimine with low molecular weight of 600, 1200 and 1800 Da, and designed as SP-PEI600, SP-PEI1200 and SP-PEI1800, respectively. SP-PEI could effectively condense plasmid DNA into nanoscale polyplexes with size range of 100–200 nm, and exhibited much lower cytotoxicity against 293T and SH-SY5Y cells than that of branched polyethylenimine (25 kDa). In vitro gene transfection demonstrated that SP-PEI/DNA complex displayed increased transfection against 293T and SH-SY5Y cells with the increase of the weight ratio of SP-PEI/DNA complex with or without 10% serum. At weight ratio of 24, SP-PEI1800/DNA polyplexes showed the highest transfection on SH-SY5Y cells, which was almost three folds higher than PEI (25 kDa). Furthermore, these SP-PEIs/DNA polyplexes could effectively transfect 293T and SH-SY5Y cells with or without 10% serum, suggesting their excellent serum tolerance.

Keywords

Soybean protein polyethylenimine cytotoxicity transfection gene delivery

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References

Park

Jeong

Kim

. Current status of polymeric gene delivery systems. Adv Drug Deliv Rev 2006; 58: 467–486.

Wong

Pelet

Putnam

. Polymer systems for gene delivery-past, present, and future. Prog Polym Sci 2007; 32: 799–837.

Lai

Tang

et al.

PEGylated block copolymers containing tertiary amine side-chains cleavable via acid-labile ortho ester linkages for pH-triggered release of DNA. Polymer 2014; 55: 2761–2771.

Liu

Huang

. Development of non-viral vectors for systemic gene delivery. J Control Release 2002; 78: 259–266.

Dalberto

Nardi

Camassola

. Mesenchymal stem cells as a platform for gene therapy protocols. Sci Prog 2010; 93: 129–140.

Boulaiz

Marchal

Prados

et al.

Non-viral and viral vectors for gene therapy. Cell Mol Biol 2004; 51: 3–22.

Tamura

Kanuma

Nakazato

et al.

A new system for regulated functional gene expression for gene therapy applications: nuclear delivery of a p16INK4A-estrogen receptor carboxy terminal fusion protein only in the presence of estrogen. Int J Oncol 2010; 36: 905–912.

Chen

et al.

Membrane immunoglobulin expressed by retroviral vector gene transfer mimics partial function of the B-cell receptor in vivo. Sci China Life Sci 2016; 59: 49–58.

Clément

Grieger

. Manufacturing of recombinant adeno-associated viral vectors for clinical trials. Mol Ther Methods Clin Dev 2016; 3: 16002–16002.

10.

Mansouri

Bellon-Echeverria

Rizk

et al.

Highly efficient baculovirus-mediated multigene delivery in primary cells. Nat Commun 2016; 7: 11529–11529.

11.

Liu

Yao

. Chitosan and its derivatives-a promising non-viral vector for gene transfection. J Control Release 2002; 83: 1–11.

12.

Cheng

Wang

Cao

et al.

Folic acid-modified soy protein nanoparticles for enhanced targeting and inhibitory. Mater Sci Eng C 2017; 71: 298–307.

13.

Elzoghby

Samy

Elgindy

. Protein-based nanocarriers as promising drug and gene delivery systems. J Control Release 2012; 161: 38–49.

14.

Riche

Williams

. Apparent digestible protein, energy and amino acid availability of three plant proteins in Florida pompano, Trachinotus carolinus L. in seawater and low-salinity water. Aquacult Nutr 2010; 16: 223–230.

15.

Chen

Zhang

Peng

et al.

Effects of nanoscale hydroxypropyl lignin on properties of soy protein plastics. J Appl Polym Sci 2006; 101: 334–341.

16.

Song

Tang

Wang

et al.

Biodegradable soy protein isolate-based materials: a review. Biomacromolecules 2011; 12: 3369–3380.

17.

Liao

Panda

et al.

Self-organized nanoparticles prepared by guanidine-and disulfide-modified chitosan as a gene delivery carrier. J Mater Chem 2011; 21: 16918–16927.

18.

Gao

Chen

et al.

Arginine-chitosan/DNA self-assemble nanoparticles for gene delivery: in vitro characteristics and transfection efficiency. Int J Pharm 2008; 359: 241–246.

19.

Ihm

Han

et al.

High transfection efficiency of poly (4-vinylimidazole) as a new gene carrier. Bioconjug Chem 2003; 14: 707–708.

20.

Wong

Sun

Zhang

Dai

et al.

PEI-g-chitosan, a novel gene delivery system with transfection efficiency comparable to polyethylenimine in vitro and after liver administration in vivo. Bioconjug Chem 2006; 17: 152–158.

21.

Akinc

Thomas

Klibanov

et al.

Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis. J Gene Med 2005; 7: 657–663.

22.

Tripathi

Gupta

Mahato

et al.

Selective blocking of primary amines in branched polyethylenimine with biocompatible ligand alleviates cytotoxicity and augments gene delivery efficacy in mammalian cells. Colloids Surf B Biointerf 2014; 115: 79–85.

23.

Bai

Wang

et al.

Reversibly Cross-linked polyplexes enable cancer-targeted gene delivery via self-promoted DNA release and self-diminished toxicity. Biomacromolecules 2015; 16: 1390–1400.

24.

Zhang

Wang

et al.

Low molecular weight PEI-based vectors via acid-labile ortho ester linkage for improved gene delivery. Macromol Biosci 2016; 16: 1175–1187.

25.

Peng

Zhong

Zhuo

. Disulfide cross-linked polyethylenimines (PEI) prepared via thiolation of low molecular weight PEI as highly efficient gene vectors. Bioconjug Chem 2008; 19: 499–506.

26.

Forrest

Koerber

Pack

. A degradable polyethylenimine derivative with low toxicity for highly efficient gene delivery. Bioconjug Chem 2003; 14: 934–940.

27.

Xun

Xiao

Zhang

et al.

Low molecular weight PEI-based polycationic gene vectors via Michael addition polymerization with improved serum-tolerance. Polymer 2015; 65: 45–54.

28.

Yao

Zha

Cheng

et al.

Folic acid-conjugated soybean protein-based nanoparticles mediate efficient antitumor ability in vitro. J Biomater Appl 2017; 31: 832–843.

29.

Athawale

Lele

. Syntheses and characterisation of graft copolymers of maize starch and methacrylonitrile. Carbohyd Polym 2000; 41: 407–416.

30.

Sun

Zeng

Meng

et al.

The influence of RGD addition on the gene transfer characteristics of disulfide-containing polyethyleneimine/DNA complexes. Biomaterials 2008; 29: 4356–4365.

31.

Suk

Suh

Choy

et al.

Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles. Biomaterials 2006; 27: 5143–5150.

32.

Luo

Saltzman

. Synthetic DNA delivery systems. Nat Biotechnol 2000; 18: 33–37.

33.

Yudovin-Farber

Domb

. Cationic polysaccharides for gene delivery. Mater Sci Eng C 2007; 27: 595–598.

34.

Wang

Zhang

et al.

Biodegradable cross-linked poly (amino alcohol esters) based on LMW PEI for gene delivery. Mol BioSyst 2011; 7: 1254–1262.

35.

Prabha

Zhou

Panyam

et al.

Size-dependency of nanoparticle-mediated gene transfection: studies with fractionated nanoparticles. Int J Pharm 2002; 244: 105–115.

36.

Corsi

Chellat

Yahia

et al.

Mesenchymal stem cells, MG63 and HEK293 transfection using chitosan-DNA nanoparticles. Biomaterials 2003; 24: 1255–1264.

37.

Sato

Ishii

Okahata

. In vitro gene delivery mediated by chitosan. Effect of pH, serum, and molecular mass of chitosan on the transfection efficiency. Biomaterials 2001; 22: 2075–2080.

38.

Thanou

Florea

Geldof

et al.

Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines. Biomaterials 2002; 23: 153–159.

39.

Zhang

Wang

et al.

Acid-labile poly (ortho ester amino alcohols) by ring-opening polymerization for controlled DNA release and improved serum tolerance. Polymer 2016; 96: 146–155.

40.

Wang

Tang

et al.

Effects of hydrophobic and hydrophilic modifications on gene delivery of amphiphilic chitosan based nanocarriers. Biomaterials 2011; 32: 4630–4638.

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