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Article ; Online: Second-Generation Polyamidoamine Dendrimer Conjugated with Oligopeptides Can Enhance Plasmid DNA Delivery In Vitro.

Kim, Seongyeon / Thuy, Le Thi / Lee, Jeil / Choi, Joon Sig

2023 Volume 28, Issue 22

Abstract: Poly(amidoamine) (PAMAM) dendrimers have attracted considerable attention in the field of gene therapy due to their flexibility in introducing different functional moieties and reduced toxicity at low generations. However, their transfection efficiency ... ...

Abstract	Poly(amidoamine) (PAMAM) dendrimers have attracted considerable attention in the field of gene therapy due to their flexibility in introducing different functional moieties and reduced toxicity at low generations. However, their transfection efficiency remains a limitation. Therefore, an essential approach for improving their transfection efficiency as gene carriers involves modifying the structure of PAMAM by conjugating functional groups around their surface. In this study, we successfully conjugated an RRHRH oligopeptide to the surface of PAMAM generation 2 (PAMAM G2) to create RRHRH-PAMAM G2. This construction aims to condense plasmid DNA (pDNA) and facilitate its penetration into cell membranes, leading to its promising potential for gene therapy. RRHRH-PAMAM G2/pDNA complexes were smaller than 100 nm and positively charged. Nano-polyplexes can enter the cell and show a high transfection efficiency after 24 h of transfection. The RRHRH-PAMAM G2 was non-toxic to HeLa, NIH3T3, A549, and MDA-MB-231 cell lines. These results strongly suggest that RRHRH-PAMAM G2 holds promise as a gene carrier for gene therapy owing to its biocompatibility and ability to deliver genes to the cell.
MeSH term(s)	Mice ; Animals ; Humans ; Dendrimers/chemistry ; NIH 3T3 Cells ; DNA/chemistry ; Plasmids/genetics ; Transfection ; Oligopeptides/chemistry
Chemical Substances	Poly(amidoamine) ; Dendrimers ; DNA (9007-49-2) ; Oligopeptides
Language	English
Publishing date	2023-11-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28227644
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Article: Nanoemulsion Composed of α-Tocopherol Succinate and Dequalinium Shows Mitochondria-Targeting and Anticancer Effects.

Thuy, Le Thi / Lee, Seulgi / Dongquoc, Viet / Choi, Joon Sig

Antioxidants (Basel, Switzerland)

2023 Volume 12, Issue 2

Abstract: Targeted drugs have been used to treat mitochondrial dysfunction-related diseases, including metabolic disorders and cancer; however, targeting and penetrating intracellular organelles remains a challenge. Dominant targeting approaches for therapeutic ... ...

Abstract	Targeted drugs have been used to treat mitochondrial dysfunction-related diseases, including metabolic disorders and cancer; however, targeting and penetrating intracellular organelles remains a challenge. Dominant targeting approaches for therapeutic delivery are detailed in many nanoemulsion studies and show the tremendous potential of targeted delivery to inhibit cancer cell growth. Dequalinium (DQA) and α-tocopherol succinate (α-TOS) are good agents for targeting mitochondria. In this study, we aimed to develop a mitochondria-targeting emulsion, using DQA and α-TOS (DTOS), for cancer treatment. DTOS emulsions of 150-170 nm in diameter were formulated using homogenization. DQA and α-TOS were used as bifunctional agents (surfactants) to stabilize the nanoemulsion and anticancer drugs. Various molar ratios of DQA and α-TOS were tested to determine the optimal condition, and DTOS 5-5 was selected for further study. The DTOS emulsion showed improved stability, as evidenced by its ability to remain stable for three years at room temperature. This stability, combined with its effective targeting of mitochondria, led to inhibition of 71.5% of HeLa cells after 24 h. The DTOS emulsion effectively inhibited spheroid growth in the 3D model, as well as prevented the growth of HeLa cells grafted onto zebrafish larvae. These results highlight the DTOS emulsion's promising potential for mitochondria-targeting and cancer treatment.
Language	English
Publishing date	2023-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12020437
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Article: Conjugation of Short Oligopeptides to a Second-Generation Polyamidoamine Dendrimer Shows Antibacterial Activity.

Kang, Namyoung / Thuy, Le Thi / Dongquoc, Viet / Choi, Joon Sig

Pharmaceutics

2023 Volume 15, Issue 3

Abstract: The growing evolution of bacterial resistance to antibiotics represents a global issue that not only impacts healthcare systems but also political and economic processes. This necessitates the development of novel antibacterial agents. Antimicrobial ... ...

Abstract	The growing evolution of bacterial resistance to antibiotics represents a global issue that not only impacts healthcare systems but also political and economic processes. This necessitates the development of novel antibacterial agents. Antimicrobial peptides have shown promise in this regard. Thus, in this study, a new functional polymer was synthesized by joining a short oligopeptide sequence (Phe-Lys-Phe-Leu, FKFL) to the surface of a second-generation polyamidoamine (G2 PAMAM) dendrimer as an antibacterial component. This method of synthesis proved simple and resulted in a high conjugation yield of the product FKFL-G2. To determine its antibacterial potential, FKFL-G2 was subsequently analyzed via mass spectrometry, a cytotoxicity assay, bacterial growth assay, colony-forming unit assay, membrane permeabilization assay, transmission electron microscopy, and biofilm formation assay. FKFL-G2 was found to exhibit low toxicity to noncancerous NIH3T3 cells. Additionally, FKFL-G2 had an antibacterial effect on
Language	English
Publishing date	2023-03-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15031005
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Article ; Online: Nanoemulsion Composed of α-Tocopherol Succinate and Dequalinium Shows Mitochondria-Targeting and Anticancer Effects

Thuy, Le Thi / Lee, Seulgi / Dongquoc, Viet / Choi, Joon Sig

Antioxidants. 2023 Feb. 10, v. 12, no. 2

2023

Abstract	Targeted drugs have been used to treat mitochondrial dysfunction-related diseases, including metabolic disorders and cancer; however, targeting and penetrating intracellular organelles remains a challenge. Dominant targeting approaches for therapeutic delivery are detailed in many nanoemulsion studies and show the tremendous potential of targeted delivery to inhibit cancer cell growth. Dequalinium (DQA) and α-tocopherol succinate (α-TOS) are good agents for targeting mitochondria. In this study, we aimed to develop a mitochondria-targeting emulsion, using DQA and α-TOS (DTOS), for cancer treatment. DTOS emulsions of 150–170 nm in diameter were formulated using homogenization. DQA and α-TOS were used as bifunctional agents (surfactants) to stabilize the nanoemulsion and anticancer drugs. Various molar ratios of DQA and α-TOS were tested to determine the optimal condition, and DTOS 5-5 was selected for further study. The DTOS emulsion showed improved stability, as evidenced by its ability to remain stable for three years at room temperature. This stability, combined with its effective targeting of mitochondria, led to inhibition of 71.5% of HeLa cells after 24 h. The DTOS emulsion effectively inhibited spheroid growth in the 3D model, as well as prevented the growth of HeLa cells grafted onto zebrafish larvae. These results highlight the DTOS emulsion’s promising potential for mitochondria-targeting and cancer treatment.
Keywords	Danio rerio ; alpha-tocopherol ; ambient temperature ; cancer therapy ; cell growth ; homogenization ; mitochondria ; models ; nanoemulsions ; neoplasm cells ; succinic acid
Language	English
Dates of publication	2023-0210
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12020437
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Article ; Online: The effect of deproteinization methods on the properties of glucosamine hydrochloride from shells of white leg shrimp (Litopenaeus vannamei) and black tiger shrimp (Penaeus monodon)

Thuy Le Thi Minh / Tran Thanh Truc / Kazufumi Osako

Ciência Rural, Vol 52, Iss

2021 Volume 1

Abstract: ABSTRACT: The effect of methods to remove protein content on the properties of glucosamine hydrochloride from the shells of white leg shrimp (Litopenaeus vannamei) and black tiger shrimp (Penaeus monodon) was investigated. Chitin from shrimp shells was ... ...

Abstract	ABSTRACT: The effect of methods to remove protein content on the properties of glucosamine hydrochloride from the shells of white leg shrimp (Litopenaeus vannamei) and black tiger shrimp (Penaeus monodon) was investigated. Chitin from shrimp shells was obtained by demineralization in 6% HCl for 12h, deproteinization by two different methods (first group soaked in 8% NaOH for 36h and second group treated in Alcalase enzyme at the concentration of 0.2% for 36h). Two group samples were converted to glucosamine hydrochloride by soaking in 36.76% HCl solution for 5h at 85 °C. The results of fourier transform infrared spectroscopy (FTIR), solubility and recovery yield analysis showed that deproteinization methods did not significantly affect the properties of glucosamine hydrochloride. However, glucosamine hydrochloride from white leg shrimp shells contained higher recovery yield and solubility than black tiger shrimp shells.
Keywords	glucosamine hydrochloride ; shrimp shells ; deproteinization method ; recovery yield ; solubility ; Agriculture ; S ; Agriculture (General) ; S1-972
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Universidade Federal de Santa Maria
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Preparation and characterization of polyamidoamine dendrimers conjugated with cholesteryl-dipeptide as gene carriers in HeLa cells.

Thuy, Le Thi / Choi, Minyoung / Lee, Minhyung / Choi, Joon Sig

Journal of biomaterials science. Polymer edition

2022 Volume 33, Issue 8, Page(s) 976–994

Abstract: Improving the transfection efficiency of non-viral carriers by using cationic polymers is a useful approach to addressing several challenges in gene therapy, such as cellular uptake, endosomal escape, and toxicity. Among the various cationic polymers, ... ...

Abstract	Improving the transfection efficiency of non-viral carriers by using cationic polymers is a useful approach to addressing several challenges in gene therapy, such as cellular uptake, endosomal escape, and toxicity. Among the various cationic polymers, polyamidoamine (PAMAM) dendrimers have been widely utilized because of the abundance of terminal functional groups, thereby enabling further functionalization and enhancing DNA condensation and internalization into cells. The combination of various functional groups is required for these PAMAM dendrimer derivatives to function appropriately for gene delivery. Herein, we synthesized PAMAM G2-HRChol by conjugating dipeptide (histidine-arginine) and cholesterol at different ratios (6% or 23%) on the surface of PAMAM dendrimer generation 2 (PAMAM G2). Both PAMAM G2-HRChol 6% and PAMAM G2-HRChol 23% have buffering capacity, leading to improved endosomal escape after entering the cells. PAMAM G2-HRChol 6% and PAMAM G2-HRChol 23% dendrimers were condensed with pDNA to form nano-polyplexes at a weight ratio of 4 (polymer/pDNA). Polyplexes are positively charged, which facilitates cellular uptake. The transfection efficiency of PAMAM G2-HRChol 6% and PAMAM G2-HRChol 23% dendrimers was similar to that of PEI 25 kDa under optimum conditions, and the cytotoxicity was much lower than that of PEI 25 kDa in HeLa cells. In addition, after apoptin gene transfection was performed, cell death ratios of 34.47% and 22.47% were observed for PAMAM G2-HRChol 6% and PAMAM G2-HRChol 23%, respectively. The results show that a suitable amount of cholesterol can improve gene transfection efficiency, and the PAMAM G2-HRChol 6% dendrimer could be a potential gene carrier in HeLa cells.
MeSH term(s)	Dendrimers/chemistry ; Dipeptides ; Gene Transfer Techniques ; HeLa Cells ; Humans ; Polyamines ; Transfection
Chemical Substances	Dendrimers ; Dipeptides ; Poly(amidoamine) ; Polyamines
Language	English
Publishing date	2022-01-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1014190-x
ISSN	1568-5624 ; 1568-5616 ; 0920-5063
ISSN (online)	1568-5624 ; 1568-5616
ISSN	0920-5063
DOI	10.1080/09205063.2022.2030657
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Article ; Online: Collaborating with AI in literature search-An important frontier.

Enomoto, Masaru / Tseng, Cheng-Hao / Hsu, Yao-Chun / Thuy, Le Thi Thanh / Nguyen, Mindie H

Hepatology communications

2023 Volume 7, Issue 12

MeSH term(s)	Artificial Intelligence
Language	English
Publishing date	2023-12-07
Publishing country	United States
Document type	Journal Article
ISSN	2471-254X
ISSN (online)	2471-254X
DOI	10.1097/HC9.0000000000000336
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Article ; Online: Transcriptomics of a cytoglobin knockout mouse: Insights from hepatic stellate cells and brain.

Porto, Elena / De Backer, Joey / Thuy, Le Thi Thanh / Kawada, Norifumi / Hankeln, Thomas

Journal of inorganic biochemistry

2023 Volume 250, Page(s) 112405

Abstract: The vertebrate respiratory protein cytoglobin (Cygb) is thought to exert multiple cellular functions. Here we studied the phenotypic effects of a Cygb knockout (KO) in mouse on the transcriptome level. RNA sequencing (RNA-Seq) was performed for the first ...

Abstract	The vertebrate respiratory protein cytoglobin (Cygb) is thought to exert multiple cellular functions. Here we studied the phenotypic effects of a Cygb knockout (KO) in mouse on the transcriptome level. RNA sequencing (RNA-Seq) was performed for the first time on sites of major endogenous Cygb expression, i.e. quiescent and activated hepatic stellate cells (HSCs) and two brain regions, hippocampus and hypothalamus. The data recapitulated the up-regulation of Cygb during HSC activation and its expression in the brain. Differential gene expression analyses suggested a role of Cygb in the response to inflammation in HSCs and its involvement in retinoid metabolism, retinoid X receptor (RXR) activation-induced xenobiotics metabolism, and RXR activation-induced lipid metabolism and signaling in activated cells. Unexpectedly, only minor effects of the Cygb KO were detected in the transcriptional profiles in hippocampus and hypothalamus, precluding any enrichment analyses. Furthermore, the transcriptome data pointed at a previously undescribed potential of the Cygb
MeSH term(s)	Animals ; Mice ; Cytoglobin/genetics ; Cytoglobin/metabolism ; Cytoglobin/pharmacology ; Gene Expression Profiling ; Globins/genetics ; Globins/metabolism ; Hepatic Stellate Cells/metabolism ; Hippocampus/metabolism ; Mice, Knockout ; Transcriptome
Chemical Substances	Cytoglobin ; Globins (9004-22-2) ; Cygb protein, mouse
Language	English
Publishing date	2023-10-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	162843-4
ISSN	1873-3344 ; 0162-0134
ISSN (online)	1873-3344
ISSN	0162-0134
DOI	10.1016/j.jinorgbio.2023.112405
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Article ; Online: Coordination-driven robust antibacterial coatings using catechol-conjugated carboxymethyl chitosan.

Thuy, Le Thi / Kim, Su Youn / Dongquoc, Viet / Kim, Younjin / Choi, Joon Sig / Cho, Woo Kyung

International journal of biological macromolecules

2023 Volume 249, Page(s) 126090

Abstract: To prevent bacterial contamination on solid surfaces, a simple yet efficient antibacterial coating was developed in a substrate-independent manner by using the catechol-conjugated carboxymethyl chitosan (CMC-DOPA). The CMC-DOPA was firstly synthesized ... ...

Abstract	To prevent bacterial contamination on solid surfaces, a simple yet efficient antibacterial coating was developed in a substrate-independent manner by using the catechol-conjugated carboxymethyl chitosan (CMC-DOPA). The CMC-DOPA was firstly synthesized via an aza-Michael reaction with methyl acrylate and the subsequent acyl substitution with dopamine. The coating strategy consists of spin-coating-assisted deposition of CMC-DOPA on polydopamine-coated substrates and coordination-driven crosslinks between catechol groups and Fe
MeSH term(s)	Chitosan ; Staphylococcus aureus ; Escherichia coli ; Anti-Bacterial Agents/pharmacology ; Dopamine/pharmacology ; Dihydroxyphenylalanine ; Coated Materials, Biocompatible/pharmacology
Chemical Substances	Chitosan (9012-76-4) ; Anti-Bacterial Agents ; Dopamine (VTD58H1Z2X) ; Dihydroxyphenylalanine (63-84-3) ; Coated Materials, Biocompatible
Language	English
Publishing date	2023-08-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2023.126090
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Article ; Online: Coordination-driven robust antibacterial coatings using catechol-conjugated carboxymethyl chitosan

Thuy, Le Thi / Kim, Su Youn / Dongquoc, Viet / Kim, Younjin / Choi, Joon Sig / Cho, Woo Kyung

International Journal of Biological Macromolecules. 2023 Aug. 03, p.126090-

2023 , Page(s) 126090–

Abstract	To prevent bacterial contamination on solid surfaces, a simple yet efficient antibacterial coating was developed in a substrate-independent manner by using the catechol-conjugated carboxymethyl chitosan (CMC-DOPA). The CMC-DOPA was firstly synthesized via aza-Michael reaction with methyl acrylate and the subsequent acyl substitution with dopamine. The coating strategy consists of spin-coating-assisted deposition of CMC-DOPA on polydopamine-coated substrates and coordination-driven crosslinks between catechol groups and Fe³⁺ ions in sequence, producing the multilayered CMC-DOPA films. The film thickness was controllable depending on the concentration of CMC-DOPA. Compared to bare controls, the CMC-DOPA coated substrates reduced the bacterial adhesion by up to 99.8 % and 96.2 % for E. coli and S. aureus, respectively. It is demonstrated that the CMC-DOPA coating can be a robust antibacterial coating across various pH environments, inhibiting bacterial adhesion by 78.7 %, 95.1 %, and 93.2 %, respectively, compared to the control, even after 7 days of acidic, physiological, and alkaline pH treatment. The current coating approach could be applied to various substrates including silicon dioxide, titanium dioxide, and polyurethane. Given its simple and versatile coating capability, we think that the coordination-driven CMC-DOPA coating could be useful for various medical devices and implants.
Keywords	Escherichia coli ; bacterial adhesion ; bacterial contamination ; catechol ; chemical reactions ; chitosan ; crosslinking ; dopamine ; pH ; polyurethanes ; silica ; titanium dioxide ; CMC-DOPA ; Antibacterial coating ; Coordination
Language	English
Dates of publication	2023-0803
Publishing place	Elsevier B.V.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2023.126090
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