• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.579-584
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• 2013

In this study, we synthesized functional dendrimer derivatives as nonviral gene delivery vectors. Poly(amidoamine) dendrimer (PAMAM, generation 4) was modified to possess functional amino acids to enhance gene transfection efficiency. PAMAM G4 derivatives conjugated with L-arginine (Arg) and ${\gamma}$-aminobutyric acid (GABA) showed higher transfection efficiency and lower cytotoxicity compared to the native PAMAM G4 dendrimer. The polyplex of the PAMAM G4 derivative/pDNA was evaluated using an agarose gel retardation assay and Picogreen reagent assay. Additionally, the MTT assay was performed to examine the cytotoxicity of synthesized polymers. All PAMAM G4 derivatives showed lower cytotoxicity than PEI25kD. Particularly, PAMAM G4-GABA-Arg displayed enhanced transfection efficiency compared to the native PAMAM G4 dendrimer.

• Bulletin of the Korean Chemical Society
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• v.32 no.2
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• pp.651-655
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• 2011

We synthesized a novel cationic dendrimer consisting of a poly(amidoamine) dendrimer (PAMAM, generation 4) backbone with both L-arginine (Arg) at the termini and 6-aminohexanoic acid (Ahx) between the original core polymer and the peripheral Arg units. The sequential chemical modification of PAMAM G4 with Ahx and Arg resulted in higher transfection efficiency with much less cytotoxicity. PAMAM G4-Ahx-Arg formed stable polyplexes at weight ratios of 8:1 or higher (polymer: plasmid DNA), and the mean polyplex diameter was $180{\pm}20nm$. PAMAM G4-Ahx-Arg showed much higher transfection ability than PAMAM G4 or PAMAM G4-Ahx. Furthermore, PAMAM G4-Ahx-Arg was much less cytotoxic than PEI25KD and PAMAM G4-Arg. In addition to Arg grafting of the PAMAM dendrimer, which endows a higher transfection capability, the addition of Ahx spacer increased dendrimer hydrophobicity, introduced flexibility into the conjugated amino acids, and reduced cytotoxicity. Overall, it appears that the concomitant modification of PAMAM with Ahx and Arg could lead to new PAMAM conjugates with better performances.

• 한국방재학회:학술대회논문집
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• 2009.02b
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• pp.157.2-157.2
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• 2009

• Journal of Life Science
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• v.30 no.10
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• pp.905-911
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• 2020

The adjuvant effect of PAMAM dendrimer G4 (PAMAM) on the induction of humoral and cellular immune responses against keyhole limpet hemocyanin (KLH) was examined. Mice were immunized subcutaneously twice at two-week intervals with KLH, with or without PAMAM dendrimer (100 ㎍/mouse), and the mice immunized with KLH+PAMAM showed significantly higher antibody titers against KLH than those immunized with KLH alone. The assay for determining the isotypes of the antibodies showed that PAMAM augmented the KLH-specific antibody titers of IgG1, IgG2a, IgG2b, IgG3, and IgM. In addition, mice immunized twice with KLH+PAMAM followed by a subcutaneous injection of KLH (20 ㎍/site) 7 weeks after the primary immunization exhibited a higher delayed-type hypersensitivity (DTH) reaction than those treated with KLH alone. In an in vitro analysis of T lymphocyte proliferation in response to KLH in week 8, the splenocytes of mice treated with KLH+PAMAM showed significantly higher proliferating activity than those treated with KLH alone, and the culture supernatants of cell cultures from mice immunized with added PAMAM dendrimer showed higher levels of KLH-specific cytokine (IL-4 and IFN-r) production. These results suggest that PAMAM dendrimer G4 possesses a potent immune-adjuvant activity for enhancing both humoral and cell-mediated immunity specific to foreign antigens.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.182-190
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• 2018

The objective of this work is to evaluate the effect of polyamidoamine (PAMAM) dendrimers on electroosmotic flow (EOF) through skin. The effect of size and concentration of dendrimer was studied, using generation 1, 4 and 7 dendrimer (G1, G4 and G7, respectively). As a marker molecule for the direction and magnitude of EOF, a neutral molecule, acetoaminophen (AAP) was used. The visualization of dendrimer permeation into the current conducting pore (CCP) of skin was made using G4-fluorescein isothiocyanate (FITC) conjugate and confocal microscopy. Without dendrimer, anodal flux of AAP was much higher than cathodal or passive flux. When G1 dendrimer was added, anodal flux decreased, presumably due to the decrease in EOF by the association of G1 dendrimer with net negative charge in CCP. As the generation increased, larger decrease in anodal flux was observed, and the direction of EOF was reversed. Small amount of methanol used for the preparation of dendrimer solution also contributed to the decrease in anodal flux of AAP. Cross-sectional view perpendicular to the skin surface by confocal laser scanning microscope (CLSM) study showed that G4 dendrimer-FITC conjugate (G4-FITC) can penetrate into the viable epidermis and dermis under anodal current. The permeation route seemed to be localized on hair follicle region. These results suggest that PAMAM dendrimers can permeate into CCP and change the magnitude and direction of EOF. Overall, we obtained a better understanding on the mechanistic insights into the electroosmosis phenomena and its role on flux during iontophoresis.

• Bulletin of the Korean Chemical Society
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• v.34 no.3
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• pp.971-974
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• 2013

• Bulletin of the Korean Chemical Society
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• v.28 no.8
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• pp.1317-1321
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• 2007

Arginine conjugated PAMAM dendrimer, PAMAM-R was modified with propylene oxide via hydroxylation of primary amines of arginine residues. About 49 amines were detected to be converted to amino alcohols by 1H NMR. The newly synthesized polymer, PAMAM-R-PO was able to completely retard pDNA from a charge ratio of 2. The average diameter of PAMAM-R-PO polyplex was found to be 242 nm at a charge ratio of 30. The Zeta-potential value of PAMAM-R-PO polyplex was able to reach 20-30 mV over a charge ratio of 10. PAMAM-R-PO indicated higher cell viability than unmodified PAMAM-R on HeLa and 293 cells because of its hydroxylated amines. Transfection experiments on 293 cells showed that the transfection efficiency of PAMAM-R-PO was found to be 1.5-1.9 times higher than that of PEI25kDa at a charge ratio of 30. The polymer eventually displayed about 2 times greater transfection efficiency than PAMAM-R at the same charge ratio in the absence of serum. Therefore, we concluded that the modification of primary amines of PAMAMR to amino alcohols gives positive effects such as reduced cytotoxicity and enhanced transfection efficiency on 293 cells for gene delivery potency of PAMAM-R.

• Bulletin of the Korean Chemical Society
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• v.24 no.8
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• pp.1197-1202
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• 2003

Patterning of biological molecules was attempted on both gold and glass using fourth generation (G4) poly(amidoamine) (PAMAM) dendrimer as an interfacing layer between solid surfaces and biomolecules. As for the patterning of avidin and anti-biotin antibody on gold, PAMAM dendrimers representing amine functionalities were firstly printed onto the 11-mercaptoundecanoic acid SAM by microcontact printing, followed by biotinylation, and reacted with fluorescence-labeled avidin or anti-biotin antibody. Fluorescence microscopic analysis revealed that the patterns of avidin and anti-biotin antibody were well constructed with the resolution of < 2 ㎛. The PAMAM dendrimers were also printed onto aldehyde-activated slide glass and reacted directly with anti-BSA antibodies, which had been oxidized with sodium periodate. As a result, distinct patterns of the anti-BSA antibodies were also obtained with a comparable edge resolution to that of avidin patterns on gold. These results clearly show that PAMAM dendrimers can be adopted as an interfacing layer for the patterning of biological molecules on solid surfaces with micrometer resolution.

• Bulletin of the Korean Chemical Society
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• v.33 no.7
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• pp.2181-2186
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• 2012

Dendrimers are a novel class of nonlinear polymers and due to their extensive applications in different fields, called versatile polymers. Polyamidoamine (PAMAM) dendrimers are one of the most important dendrimers that have many applications in nanobiotechnology and industry. Generally aldehyde terminated dendrimers are prepared by activation of amine terminated dendrimers by glutaraldehyde which has two problems, toxicity and possibility of crosslink formation. In this study, novel aldehyde-terminated PAMAM dendrimer was prepared and used for covalent immobilization of trypsin by the aim of finding a special reagent which can prevent crosslinking and deactivation of the enzyme. For this purpose aminoacetaldehydedimethylacetal (AADA) was used as spacer group between aldehyde-terminated PAMAM and trypsin.The findings of this study showed that immobilization of trypsin not only resulted higher optimal temperature, but also increased the thermal stability of the immobilized enzyme in comparison to the free enzyme.

• Bulletin of the Korean Chemical Society
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• v.35 no.4
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• pp.1036-1042
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• 2014

In this study, we introduced the RRLR oligopeptide sequences on the surface of polyamidoamine (PAMAM) dendrimer and characterized the physical properties and gene carrier activity of the novel polymer using HEK 293, NIH3T3, and HeLa cells. The RRLR peptide sequences were derived from a mouse fibroblast growth factor 3 (FGF3) protein containing a bipartite NLS motif. The entire sequence of FGF3 is RLRRDAGGRGGVYEHLGGAPRRRK and it has two functional sequences RLRR and RRRK at N-terminus and C-terminus, respectively. In particular, PAMAM G4-RRLR conferred enhanced transfection efficiency and lower cytotoxicity compared with those of PEI 25 kDa, PAMAM G4-R, and PAMAM G4 in various cell lines. These results suggest that the introduction of N-terminal oligopeptides of FGF3 on the surface of PAMAM holds promise as an effective non-viral gene delivery carrier for gene therapy.