Method for the Instant In-Flight Manufacture of Black Phosphorus to Assemble Core@Shell Nanocomposites for Targeted Photoimmunotherapy

Nguyen, Hanh Thuy,Byeon, Jeong Hoon,Phung, Cao Dai,Pham, Le Minh,Ku, Sae Kwang,Yong, Chul Soon,Kim, Jong Oh American Chemical Society 2019 ACS APPLIED MATERIALS & INTERFACES Vol.11 No.28

<P>Inorganic nanomaterial (INM)-based combination cancer therapies have been extensively employed over the past two decades because of their benefits over traditional chemo- and radiotherapies. However, issues regarding the toxicity and accumulation of INMs in the body have arisen. This problem may be improved through the use of biodegradable or disintegrable nanosystems such as black phosphorus (BP). Challenges to the manufacture of fully nanodimensional BP remain. In addition, improvements in recently developed cancer immunotherapies require their incorporation with drugs, targeting agents, and delivery vehicles. With these needs in mind, this study develops a method for instant in-flight manufacture of nanodimensional BP using plug-and-play devices for subsequent assembly of photoimmunotherapeutic core@shell composites containing mutated B-raf inhibitors (dabrafenib), immune checkpoint inhibitors (PD-L1), and cancer-targeting antibodies (CXCR4). The resulting nanocomposites exhibited cancer targetability and regulatability of PD-L1 expression both in vitro and in vivo. These activities were further increased upon near-infrared irradiation due to the incorporation of a phototherapeutic component. These results suggest that these nanocomposites are promising as a new class of advanced cancer therapeutic agents.</P> [FIG OMISSION]</BR>

Medicinal Chemistry : RESEARCH ARTICLE ; Enhancing the in vitro anti-cancer efficacy of artesunate by loading into poly-D,L-lactide-co-glycolide (PLGA) nanoparticles

( Hanh Thuy Nguyen ),( Tuan Hiep Tran ),( Jong Oh Kim ),( Chul Soon Yong ),( Chien Ngoc Nguyen ) 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-

Artesunate (ART).a well-known anti-malarial agent is also known to have potential anti-proliferative activities but its instability, poor aqueous solubility, and lack of relevant studies have limited its application as an effective anti-cancer drug. To overcome these problems, ART was loaded in poly (lactic-co-glycolic) acid (PLGA) nanoparticles using oil/water emulsion evaporation method. PLGA nanoparticles with small particle size and high entrapment efficiency were obtained. The PLGA nanoparticles were optimized by evaluating the effects of several formulation parameters on physicochemical properties of nanoparticles. The in vitro cytotoxicity of blank PLGA, free ART, and ART-PLGA on 3 human cancer cell lines viz. A549, SCC-7, and MCF-7 was conducted using MTT assay. The particles showed nanometric size (*170 nm), large entrapment efficiency (up to 83.4 %), and excellent stability (evaluated for 1 month) after lyophilization with 5 % mannitol. ART was dispersed inside particle core allowing a sustained release up to 48 h. The in vitro cytotoxicity results demonstrated strong activity of ART against cancer cell lines. The ART-PLGA formulation significantly reduced cell viability than the free ART. The formulation of ART loaded PLGA nanoparticles supported a potential application of ART as an anticancer agent.

Targeted co-delivery of polypyrrole and rapamycin by trastuzumab-conjugated liposomes for combined chemo-photothermal therapy

Nguyen, Hanh Thuy,Tran, Tuan Hiep,Thapa, Raj Kumar,Phung, Cao Dai,Shin, Beom Soo,Jeong, Jee-Heon,Choi, Han-Gon,Yong, Chul Soon,Kim, Jong Oh Elsevier 2017 International journal of pharmaceutics Vol.527 No.1

<P><B>Abstract</B></P> <P>Trastuzumab is a therapeutic monoclonal antibody that selectively recognizes HER2/neu receptor for targeting breast cancers. In this study, we aimed to present a strategy to combine chemo and phototherapy and targeted delivery via monoclonal antibody for enhanced anticancer effects. We co-loaded a chemotherapeutic agent, rapamycin, and a photosensitizer, polypyrrole, in trastuzumab-conjugated liposomes (LRPmAb) for combined chemo-photothermal therapy. LRPmAb had small size (172.2±9.6nm), narrow distribution, and negative ζ-potential (−12.0±0.3mV). In addition, LRPmAb showed pH- and temperature-dependent release profiles. LRPmAb showed significantly enhanced uptake in BT-474 cells, a natural HER2/neu expressing cell line. We found that these LRPmAb were effective in delivering rapamycin and showed higher therapeutic efficacy in breast cancer cells overexpressing HER2/neu receptors compared with cells that did not overexpress these receptors. Furthermore, LRPmAb showed synergistic activity against rapamycin-sensitive and resistant cell lines in vitro. These findings indicated that LRPmAb-mediated drug delivery could improve the therapeutic efficacy against breast cancer and overcome drug resistance.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Transferrin-conjugated pH-sensitive platform for effective delivery of porous palladium nanoparticles and paclitaxel in cancer treatment

Nguyen, Hanh Thuy,Soe, Zar Chi,Yang, Kwan Yeol,Phung, Cao Dai,Nguyen, Lan Thi-Trinh,Jeong, Jee-Heon,Jin, Sung Giu,Choi, Han-Gon,Ku, Sae Kwang,Yong, Chul Soon,Kim, Jong Oh Elsevier 2019 Colloids and surfaces. B, Biointerfaces Vol.176 No.-

<P><B>Abstract</B></P> <P>Porous palladium (Pd) nanoparticles have garnered great research attention due to their potential anticancer activity and photothermal effect. In this study, a transferrin-conjugated pH-sensitive platform (Tf-PPP), comprising porous Pd nanoparticles (PdNPs) and paclitaxel (PTX), was successfully developed for combined chemo-phototherapy. Tf-PPPs have a small size of 164.6 ± 8.7 nm, PDI of 0.278 ± 0.029, and negative charge (-13.2 ± 1.8 mV). Poly(acrylic acid)-poly(ethylene oxide) (PAA-PEO), a pH sensitive polymer, was used to achieve pH-dependent drug release from nanoparticles. Transferrin (Tf) conjugated on the surface of nanoplatforms could enhance the cellular uptake and prolong nanoparticle accumulation in the tumor site. The combination of phototherapy induced by PdNPs and chemotherapeutic agent (PTX) could exhibit synergistic anticancer activities. Consistent findings were observed in both <I>in vitro</I> experiments including cytotoxicity, live/dead assay, and assessment of apoptotic protein levels, and <I>in vivo</I> antitumor study in MCF-7 tumor-bearing mice, with results decreasing in the following order: Tf-PPPs + NIR > Tf-PPPs > PPPs + NIR > PPPs > PTX > PdNPs. These findings suggest that the administration of Tf-PPPs, followed by NIR irradiation could be a promising strategy in the treatment of cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Transferrin-conjugated pH-sensitive platform was prepared for delivery of porous palladium nanoparticles and paclitaxel. </LI> <LI> The formulation exhibited higher drug release profiles at the acid environment with NIR exposure. </LI> <LI> <I>In vitro</I> studies showed high uptake and high cytotoxicity, especially in combination with NIR laser treatment. </LI> <LI> <I>In vivo</I> antitumor study showed synergistic anticancer activity with minimal adverse effects. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Transferrin-conjugated pH-sensitive platform for effective delivery of porous palladium nanoparticles and paclitaxel.</P> <P>[DISPLAY OMISSION]</P>

Barriers to Derivative Accounting Disclosure: The Case of Vietnamese Firms

NGUYEN, Hanh Thi Hong,TRAN, Ngoc Minh,NGUYEN, Quyen Le Hoang Thuy To Korea Distribution Science Association 2020 The Journal of Asian Finance, Economics and Busine Vol.7 No.10

This paper explores the barriers to derivative accounting disclosures in Vietnamese companies and ranks their relative importance for effective and efficient remedies. The Delphi technique was applied to get agreement of panel of experts on the measurement of factors hindering disclosure. Unstructured questionnaires were first sent to twelve experts who had both practical experience and academic knowledge in the field to get ideas on the obstructions to derivatives disclosure. The structured questionnaire was designed to get their agreement on barriers to derivative accounting disclosures. The data analysis with mean, median, mode, standard deviation, and quartile has been implemented to ensure the unanimity. Market-related factors, legislation, accountants' attributes, managers' attributes, information technology and communication, and on-site training were the six major obstacles agreed upon by the experts during their in-depth interviews. Then, these factors were ranked by applying the analytical hierarchy process (AHP). The findings confirmed the priority of information technology and communication, which held the greatest weight. Legislation ranked second, followed by market-related factors and on-site training, which explained the impediments to derivatives disclosure. Managers' and accountants' attributes had the least contribution to the barriers to derivative disclosures. The results have important implications for actions to enhance corporate derivative disclosures in Vietnam.

CD9 monoclonal antibody-conjugated PEGylated liposomes for targeted delivery of rapamycin in the treatment of cellular senescence

Nguyen, Hanh Thuy,Thapa, Raj Kumar,Shin, Beom Soo,Jeong, Jee-Heon,Kim, Jae-Ryong,Yong, Chul Soon,Kim, Jong Oh IOP Pub 2017 Nanotechnology Vol.28 No.9

<P>Premature cellular senescence refers to the state of irreversible cell cycle arrest due to DNA damage or other stresses. In this study, CD9 monoclonal antibody (CD9mAb) was successfully conjugated to the surface of PEGylated liposomes for targeted delivery of rapamycin (LR-CD9mAb) to overcome senescence of CD9 receptor-overexpressing cells. LR-CD9mAb has a small particle size (143.3?±?2.4 nm), narrow size distribution (polydispersity index: 0.220?±?0.036), and negative zeta potential (−14.6?±?1.2 mV). The uptake of CD9-targeted liposomes by premature senescent human dermal fibroblasts (HDFs) was higher than that by young HDFs, as displayed by confocal microscopic images. The senescence might not be reversed by treatment with rapamycin; however, the drug promoted cell proliferation and reduced the number of cells that expressed the senescence-associated-<I>β</I>-galactosidase (SA-<I>β</I>-gal). These effects were further confirmed by cell viability, cell cycle, and Western blotting analyses. Moreover, CD9-targeted liposomes showed better anti-senescence activity, in comparison with free rapamycin or the conventional liposomal formulation, suggesting the potential application of this system in further <I>in vivo</I> studies.</P>

Enhancing the in vitro anti-cancer efficacy of artesunate by loading into poly-D,L-lactide-co-glycolide (PLGA) nanoparticles

Hanh Thuy Nguyen,Tuan Hiep Tran,김종오,용철순,Chien Ngoc Nguyen 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.5

Artesunate (ART)—a well-known anti-malarialagent is also known to have potential anti-proliferativeactivities but its instability, poor aqueous solubility, andlack of relevant studies have limited its application as aneffective anti-cancer drug. To overcome these problems,ART was loaded in poly (lactic-co-glycolic) acid (PLGA)nanoparticles using oil/water emulsion evaporationmethod. PLGA nanoparticles with small particle size andhigh entrapment efficiency were obtained. The PLGAnanoparticles were optimized by evaluating the effects ofseveral formulation parameters on physicochemical propertiesof nanoparticles. The in vitro cytotoxicity of blankPLGA, free ART, and ART-PLGA on 3 human cancer celllines viz. A549, SCC-7, and MCF-7 was conducted usingMTT assay. The particles showed nanometric size(*170 nm), large entrapment efficiency (up to 83.4 %),and excellent stability (evaluated for 1 month) afterlyophilization with 5 % mannitol. ART was dispersedinside particle core allowing a sustained release up to 48 h. The in vitro cytotoxicity results demonstrated strongactivity of ART against cancer cell lines. The ART-PLGAformulation significantly reduced cell viability than the freeART. The formulation of ART loaded PLGA nanoparticlessupported a potential application of ART as an anticancer agent.

Multifunctional nanoparticles as somatostatin receptor-targeting delivery system of polyaniline and methotrexate for combined chemo–photothermal therapy

Nguyen, Hanh Thuy,Phung, Cao Dai,Thapa, Raj Kumar,Pham, Tung Thanh,Tran, Tuan Hiep,Jeong, Jee-Heon,Ku, Sae Kwang,Choi, Han-Gon,Yong, Chul Soon,Kim, Jong Oh Elsevier 2018 ACTA BIOMATERIALIA Vol.68 No.-

<P><B>Abstract</B></P> <P>Lanreotide (LT), a synthetic analog of somatostatin, has been demonstrated to specifically bind to somatostatin receptors (SSTRs), which are widely overexpressed in several types of cancer cells. In this study, we incorporated a chemotherapeutic agent, methotrexate (MTX), and a photosensitizer material, polyaniline (PANI), into hybrid polymer nanoparticles (NPs), which could target cancer cells after conjugation with LT (LT-MTX/PANI NPs). The successful preparation of LT–MTX/PANI NPs was confirmed by a small particle size (187.9 ± 3.2 nm), a polydispersity index of 0.232 ± 0.011, and a negative ζ potential of −14.6 ± 1.0 mV. Notably, LT-MTX/PANI NPs showed a greater uptake into SSTR-positive cancer cells and thereby better inhibited cell viability and induced higher levels of apoptosis than MTX, PANI NP, and MTX/PANI NP treatments did. In addition, the heat associated with the burst drug release induced by near-infrared (NIR) irradiation resulted in remarkably enhanced cell apoptosis, which was confirmed by an increase in the expression levels of apoptotic marker proteins. In agreement with the <I>in vitro</I> results, the administration of the SSTR-targeting NPs, followed by NIR exposure, to xenograft tumor-bearing mice resulted in an improved suppression of tumor development compared to that shown by MTX, PANI NPs, and MTX/PANI NPs, as well as by LT-MTX/PANI NPs without photothermal therapy. Thus, the SSTR-targeting NPs could be a promising delivery system for the effective treatment of SSTR-positive cancers.</P> <P><B>Statement of significance</B></P> <P>Somatostatin receptors are widely overexpressed in several types of cancer cells. In this study, we designed nanoparticles for targeted delivery of chemotherapeutic agents to tumor sites by conjugating hybrid polymers with a synthetic analog of somatostatin, specifically binding to somatostatin receptors. In addition, a photosensitizer material, polyaniline, was incorporated into the nanoparticles for combined chemo–photothermal therapy. The results demonstrated clear advantages of the newly designed targeted nanoparticles over their non-targeted counterparts or a free chemotherapeutic drug in inhibiting the viability of cancer cells <I>in vitro</I> and targeting/suppressing the tumor growth in an animal xenograft model. The study suggests that the designed nanoparticles are a promising delivery system for the effective treatment of somatostatin receptor-positive cancers.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Antibiotic-Resistant Gram-negative Bacteria Carriage in Healthcare Workers Working in an Intensive Care Unit

Duong Bich Thuy,Duong Minh Cuong,Campbell James,Nguyen Van Minh Hoang,Nguyen Huu Hien,Bui Thi Bich Hanh,Nguyen Van Vinh Chau,McLaws Mary-Louise 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.3

Little is known about antibiotic-resistant Gram-negative bacteria (GNB) intestinal carriage among healthcare workers (HCWs) in Vietnam. All HCWs at a tertiary intensive care units were asked to undertake weekly rectal swabs. Among 40 participants, 65% (26/40) carried extended spectrum β-lactamases (ESBL)/AmpC β-lactamase-producing Escherichia coli. Two HCWs colonized with ESBL/AmpC β-lactamase-producing Klebsiella pneumoniae. One HCW colonized with Acinetobacter baumannii. No one carried Pseudomonas spp.. A quarter (10/40) of HCWs were identified as persistent and frequent carriers. There is an urgent need to screen antibiotic-resistant GNB among HCWs and improve HCWs’ hand hygiene compliance to reduce the transmission of antibiotic-resistant GNB in the hospital.

Targeted and controlled drug deliveryl system loading artersunate for effective chemotherapy on CD44 overxpressing cancer cells

( Tuan Hiep Tran ),( Tuan Duc Nguyen ),( Han Van Nguyen ),( Hanh Thuy Nguyen ),( Jong Oh Kim ),( Chul Soon Yong ),( Chien Ngoc Nguyen ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-

Polyro.t-lactic-co-glycolic acid) (PLGA) nanoparticles with negative surface charge were reversed to positive by cationic surfactant-DDAB before being coated with an anionic polymer, hyaluronic acid, to improve their site-specific intracellular delivery against CD44 receptor overexpressing cancer cells. Incorporating artesunate (ART)-a promising anticancer drug into PLGA/HA nanoparticles, is expected not only to overcome its poor aqueous solubility and stability but also enhance the activities. The obtained particles were characterized by dynamic light scattering, zeta potential measurements, and transmission electron microscopy (TEM). Cancer cell internalization of the NPs was evaluated by flow cytometry and cytotoxicity of the NPs was tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. PLGA/HA nanoparticles showed greater extent of cellular uptake to SCC-7 and MCF-7 cells, indicating their affinity with CD44 receptor-mediated endocytosis. Almost 60 % of ART was released into the outer media after 48 h. In vitro fluorescence sorting demonstrated that PLGA/HA had highly efficient targeting and accumulation into CD44 receptor overexpression cells. The significant reduction in cell viability as well as greater induction of apoptosis suggested a potential in anticancer therapy of ART loaded PLGA/HA.