Functional Cycloamylose as a Polysaccharide-Based Biomaterial: Application in a Gene Delivery System

Toita, Sayaka; Morimoto, Nobuo; Akiyoshi, Kazunari

doi:10.1021/bm901109z

Cited by 57 publications

(44 citation statements)

References 30 publications

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“…Hyperbranched cationic glycogen derivatives as efficient gene vectors the DMAPA-Glyp/pDNA and the AEPZ-Glyp/pDNA complexes, respectively (lanes [3][4][5][6][7][8][9][10][11][12][13][14]. This demonstrated that the glycogen derivatives exhibited distinct protective effects against DNase I.…”

mentioning

confidence: 85%

“…3,12 Glycogen (0.62 mmol glucose units, 0.1000 g) was dissolved in 10 mL of anhydrous DMSO, and subsequently activated by the addition of CDI (5.58 mmol, 0.9045 g). The resulting mixture was then stirred for 1 hour in a nitrogen atmosphere at room temperature.…”

Section: Synthesis and Characterization Of Hyperbranched Cationic Glymentioning

confidence: 99%

“…3,12 From the FTIR spectra shown in Figure 2A, it was clear that a strong absorption peak of glycogen derivatives at 1,709 cm −1 was different from that of glycogen, which could be assigned to the −C=O vibration of the carbamate groups. 18 Furthermore, the absorption peaks at 1,540-1,550 and 1,250-1,270 cm −1 were attributed to the −NH− and C−N vibrations of the carbamate groups, respectively.…”

Section: Synthesis Of Hyperbranched Cationic Glycogen Derivativesmentioning

confidence: 99%

“…Recent work has established that the architecture of cationic polymers affects the stability, delivery, and transfection efficiency of their complexes with deoxyribonucleic acid (DNA). [3][4][5][6][7][8] In contrast to linear cationic polymers, hyperbranched cationic polymers exhibit higher levels of gene expression, probably because of the following two factors: 1) they present compact and globular structures in combination with a significant number and variety of different amine groups, which are advantageous for the binding and condensation of DNA into compact particles, resulting in improved protection and endocytosis of DNA; [4][5][6][7] and 2) they exhibit better proton-buffer capacity, which is beneficial for the escape of DNA from endosomes. 4,8 Synthetic hyperbranched cationic polymers, however, such as branched polyethyleneimine (bPEI) and poly(amidoamine) (PAMAM) dendrimers, are still associated with cytotoxicity, biocompatibility, and biodegradability issues, which need to be overcome to allow for in vivo application.…”

Section: Introductionmentioning

confidence: 99%

“…11 Following amination, various cationized polysaccharide derivatives have been designed and synthesized as gene-delivery vectors, with high transfection efficiency. 3,[11][12][13][14][15][16][17][18] Glycogen is a storage form of glucose that occurs predominantly in the liver and skeletal muscles of mammalian and shellfish species. 19 It is a natural hyperbranched polysaccharide with high weight-average molecular weight: about 10 6 -10 7 g/mol.…”

Section: Introductionmentioning

confidence: 99%

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An efficient nonviral gene-delivery vector based on hyperbranched cationic glycogen derivatives

Liu¹,

Ren²,

Liu³

et al. 2014

IJN

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Background The purpose of this study was to synthesize and evaluate hyperbranched cationic glycogen derivatives as an efficient nonviral gene-delivery vector. Methods A series of hyperbranched cationic glycogen derivatives conjugated with 3-(dimethylamino)-1-propylamine (DMAPA-Glyp) and 1-(2-aminoethyl) piperazine (AEPZ-Glyp) residues were synthesized and characterized by Fourier-transform infrared and hydrogen-1 nuclear magnetic resonance spectroscopy. Their buffer capacity was assessed by acid–base titration in aqueous NaCl solution. Plasmid deoxyribonucleic acid (pDNA) condensation ability and protection against DNase I degradation of the glycogen derivatives were assessed using agarose gel electrophoresis. The zeta potentials and particle sizes of the glycogen derivative/pDNA complexes were measured, and the images of the complexes were observed using atomic force microscopy. Blood compatibility and cytotoxicity were evaluated by hemolysis assay and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, respectively. pDNA transfection efficiency mediated by the cationic glycogen derivatives was evaluated by flow cytometry and fluorescence microscopy in the 293T (human embryonic kidney) and the CNE2 (human nasopharyngeal carcinoma) cell lines. In vivo delivery of pDNA in model animals (Sprague Dawley rats) was evaluated to identify the safety and transfection efficiency. Results The hyperbranched cationic glycogen derivatives conjugated with DMAPA and AEPZ residues were synthesized. They exhibited better blood compatibility and lower cytotoxicity when compared to branched polyethyleneimine (bPEI). They were able to bind and condense pDNA to form the complexes of 100–250 nm in size. The transfection efficiency of the DMAPA-Glyp/pDNA complexes was higher than those of the AEPZ-Glyp/pDNA complexes in both the 293T and CNE2 cells, and almost equal to those of bPEI. Furthermore, pDNA could be more safely delivered to the blood vessels in brain tissue of Sprague Dawley rats by the DMAPA-Glyp derivatives, and then expressed as green fluorescence protein, compared with the control group. Conclusion The hyperbranched cationic glycogen derivatives, especially the DMAPA-Glyp derivatives, showed high gene-transfection efficiency, good blood compatibility, and low cyto toxicity when transfected in vitro and in vivo, which are novel potential nonviral gene vectors.

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