• Title/Summary/Keyword: Cell delivery

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Microguidewire Looping to Traverse Stented Parent Arteries of Intracranial Aneurysms

  • Cho, Young Dae;Rhim, Jong Kook;Yoo, Dong Hyun;Kang, Hyun-Seung;Kim, Jeong Eun;Han, Moon Hee
    • Journal of Korean Neurosurgical Society
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    • v.60 no.2
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    • pp.262-268
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    • 2017
  • Objective : Stents are widely used in coil embolization of intracranial aneurysms, but on occasion, a microcatheter must traverse a stented segment of artery (so-called trans-cell technique) to select an aneurysm, or double stenting may necessary. In such situations, microguidewire passage and microcatheter delivery through a tortuous stented parent artery may pose a technical challenge. Described herein is a microguidewire looping technique to facilitate endovascular navigation in these circumstances. Methods : To apply this technique, the microguidewire tip is looped before entering the stented parent artery and then advanced distally past the stented segment, with the loop intact. Rounding of the tip prevents interference from stent struts during passage. A microcatheter is subsequently passed into the stented artery for positioning near the neck of aneurysm, with microguidewire assistance. The aneurysm is then selected, steering the microcatheter tip (via inner microguidewire) into the dome. Results : This technique proved successful during coil embolization of nine saccular intracranial aneurysms (internal carotid artery [ICA], 6; middle cerebral artery, 2; basilar tip, 1), performing eight trans-cell deliveries and one additional stenting. Selective endovascular embolization was enabled in all patients, resulting in excellent clinical and radiologic outcomes, with no morbidity or mortality directly attributable to microguidewire looping. Conclusion : Microguidewire looping is a reasonable alternative if passage through a stented artery is not feasible by traditional means, especially at paraclinoid ICA sites.

Oral and IV Dosages of Doxorubicin-Methotrexate loaded-Nanoparticles Inhibit Progression of Oral Cancer by Down-Regulation of Matrix Methaloproteinase 2 Expression in Vivo

  • Abbasi, Mehran Mesgari;Jahanban-Esfahlan, Rana;Monfaredan, Amir;Seidi, Khaled;Hamishehkar, Hamed;Khiavi, Monir Moradzadeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10705-10711
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    • 2015
  • Oral cancer is one of the most common and lethal cancers in the world. Combination chemotherapy coupled with nanoparticle drug delivery holds substantial promise in cancer therapy. This study aimed to evaluate the efficacy and safety of two dosages of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NPs) with attention to the MMP-2 mRNA profile in a 4-nitroquinoline-1-oxide induced oral squamous cell carcinoma (OSCC) model in the rat. Our results showed that both IV and oral dosages of DOX-MTX NP caused significant decrease in mRNA levels of MMP-2 compared to the untreated group (p<0.003). Surprisingly, MMP-2 mRNA was not affected in DOX treated compared to cancer group (p>0.05). Our results indicated that IV dosage of MTX-DOX is more effective than free DOX (12 fold) in inhibiting the activity of MMP-2 in OSCCs (P<0.001). Furthermore, MMP-2 mRNA expression in the DOX-MTX treated group showed a significant relation with histopathological changes (P=0.011). Compared to the untreated cancer group, we observed no pathological changes and neither a significant alteration in MMP-2 amount in either of healthy controls that were treated with oral and IV dosages of DOX-MTX NPs whilst cancer group showed a high level of MMP-2 expression compared to healthy controls (p<0.001).Taking together our results indicate that DOX-MTX NPs is a safe chemotherapeutic nanodrug that its oral and IV forms possess potent anti-cancer properties on aggressive tumors like OSCC, possibly by affecting the expression of genes that drive tumor invasion and metastasis.

Intracellular Electrical Stimulation on PC-12 Cells through Vertical Nanowire Electrode

  • Kim, Hyungsuk;Kim, Ilsoo;Lee, Jaehyung;Lee, Hye-young;Lee, Eungjang;Jeong, Du-Won;Kim, Ju-Jin;Choi, Heon-Jin
    • Proceedings of the Korean Vacuum Society Conference
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    • 2014.02a
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    • pp.407-407
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    • 2014
  • Nanotechnology, especially vertically grown silicon nanowires, has gotten great attentions in biology due to characteristics of one dimensional nanostructure; controllable synthetic structure such as lengths, diameters, densities. Silicon nanowires are promising materials as nanoelectrodes due to their highly complementary metal-oxide-semiconductor (CMOS) - and bio-compatibility. Silicon nanowires are so intoxicated that are effective for bio molecular delivery and electrical stimulation. Vertical nanowires with integrated Au tips were fabricated for electrical intracellular interfacing with PC-12 cells. We have made synthesized two types of nanowire devices; one is multi-nanowires electrode for bio molecular sensing and electrical stimulation, and the other is single-nanowires electrode respectively. Here, we demonstrate that differentiation of Nerve Growth Factor (NGF) treated PC-12 cells can be promoted depending on different magnitudes of electrical stimulation and density of Si NWs. It was fabricated by both bottom-up and top-down approaches using low pressure chemical vapor deposition (LPCVD) with high vacuuming environment to electrically stimulate PC-12 cells. The effects of electrical stimulation with NGF on the morphological differentiation are observed by Scanning Electron Microscopy (SEM), and it induces neural outgrowth. Moreover, the cell cytosol can be dyed selectively depending on the degree of differentiation along with fluorescence microscopy measurement. Vertically grown silicon nanowires have further expected advantages in case of single nanowire fabrication, and will be able to expand its characteristics to diverse applications.

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Production of the polyclonal subunit C protein antibody against Aggregatibacter actinomycetemcomitans cytolethal distending toxin

  • Lee, Su-Jeong;Park, So-Young;Ko, Sun-Young;Ryu, So-Hyun;Kim, Hyung-Seop
    • Journal of Periodontal and Implant Science
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    • v.38 no.sup2
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    • pp.335-342
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    • 2008
  • Purpose: Cytolethal distending toxin (CDT) considered as a key factor of localized aggressive periodontitis, endocarditis, meningitis, and osteomyelitis is composed of five open reading frames (ORFs). Among of them, the individual role of CdtA and CdtC is not clear; several reports presents that CDT is an AB2 toxin and they enters the host cell via clathrin-coated pits or through the interaction with GM3 ganglioside. So, CdtA, CdtC, or both seem to be required for the delivery of the CdtB protein into the host cell. Moreover, recombinant CDT was suggested as good vaccine material and antibody against CDT can be used for neutralization or for a detection kit. Materials and Methods: We constructed the pET28a-cdtC plasmid from Aggregatibacter actinomycetemcomitans Y4 by genomic DNA PCR and expressed in BL21 (DE3) Escherichia coli system. We obtained the antibody against the recombinant CdtC in mice system. Using the anti-CdtC antibody, we test the native CdtC detection by ELISA and Western Blotting and confirm the expression time of native CdtC protein during the growth phase of A. actinomycetemcomitans. Results: In this study we reconstructed CdtC subunit of A. actinomycetemcomitans Y4 and generated the anti CdtC antibody against recombinant CdtC subunit expressed in E. coli system. Our anti CdtC antibody can be interacting with recombinant CdtC and native CDT in ELISA and Western system. Also, CDT holotoxin existed at 24h but not at 48h meaning that CDT holotoxin was assembled at specific time during the bacterial growth. Conclusion: In conclusion, we thought that our anti CdtC antibody could be used mucosal adjuvant or detection kit development, because it could interact with native CDT holotoxin.

All-trans Retinoic Acid-Associated Low Molecular Weight Water-Soluble Chitosan N anoparticles Based on Ion Complex

  • Kim Dong-Gon;Choi Changyong;Jeong Young-Il;Jang Mi-Kyeong;Nah Jae-Woon;Kang Seong-Koo;Bang Moon-Soo
    • Macromolecular Research
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    • v.14 no.1
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    • pp.66-72
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    • 2006
  • The purpose of this study is to develop novel nanoparticles based on polyion complex formation between low molecular weight water-soluble chitosan (LMWSC) and all-trans retinoic acid (atRA). LMWSC nanoparticles encapsulating atRA based on polyion complex were prepared by mixing of atRA into LMWSC aqueous solution using ultrasonication. In FTIR spectra, the carbonyl group of atRA at 1690 $cm^{-1}$ disappeared or decreased when ion complexes were formed between LMWSC and atRA. In ${1}^H$ NMR spectra, specific peaks of atRA disappeared when atRA-encapsulated LMWSC (RAC) nanoparticles were reconstituted into $D_{2}O$ while specific peaks both of atRA and LMWSC appeared in $D_{2}O$/DMSO (1/3, v/v) mixture. XRD patterns also showed that the crystal peaks of atRA were disappeared by encapsulation into LMWSC nanoparticles. LMWSC nanoparticles encapsulating atRA have spherical shapes with particle size below 200 nm. The mechanism of encapsulation of atRA into LMWSC nanoparticles was thought to be an ion complex formation between LMWSC and atRA. LMWSC nanoparticles showed high atRA loading efficiency over 90$\%$ (w/w). AtRA was continuously released from nanoparticles over 10 days. In in vitro cell cytotoxicity test, free atRA showed higher cytotoxic effect against CT 26 colon carcinoma cell line on 1 day. However, RAC nanoparticles showed similar cytotoxicity against CT 26 cells on 2 day. These results suggest the potential for the introduction of LMWSC nanoparticles into various biomedical fields such as drug delivery.

Measurement of Phase Behavior for Dextran/DMSO/scCO2 System (Dextran/DMSO/초임계 CO2계의 상거동 측정)

  • Rho, Seon-Gyun;Kang, Dong-Yuk;Kang, Choon-Hyoung
    • Korean Chemical Engineering Research
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    • v.55 no.2
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    • pp.225-229
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    • 2017
  • Micron-sized dextran particles, which now attract wide attention as a promising drug delivery systems, can be prepared via the supercritical anti-solvent (SAS) process. In SAS process, dextran particles are obtained as a result of recrystallization of dissolved dextran in dimethyl sulfoxide (DMSO) on addition of supercritical $CO_2$ as an anti-solvent. In this work, with an intention to provide information on the feasible operating conditions of the process, the phase behavior of Dexran/DMSO/$CO_2$ is observed by measuring the cloud point in favor of a variable volume cell. From the experimental study, it is concluded that a feasible operating condition of the SAS process for preparation of dextran particles would be 300.15 K~330.15 K and 90 bar~130 bar, respectively, and solute concentration ranges from 5mg/ml to 20 mg/ml.

Dosimetric comparison of axilla and groin radiotherapy techniques for high-risk and locally advanced skin cancer

  • Mattes, Malcolm D.;Zhou, Ying;Berry, Sean L.;Barker, Christopher A.
    • Radiation Oncology Journal
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    • v.34 no.2
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    • pp.145-155
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    • 2016
  • Purpose: Radiation therapy targeting axilla and groin lymph nodes improves regional disease control in locally advanced and high-risk skin cancers. However, trials generally used conventional two-dimensional radiotherapy (2D-RT), contributing towards relatively high rates of side effects from treatment. The goal of this study is to determine if three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or volumetric-modulated arc therapy (VMAT) may improve radiation delivery to the target while avoiding organs at risk in the clinical context of skin cancer regional nodal irradiation. Materials and Methods: Twenty patients with locally advanced/high-risk skin cancers underwent computed tomography simulation. The relevant axilla or groin planning target volumes and organs at risk were delineated using standard definitions. Paired t-tests were used to compare the mean values of several dose-volumetric parameters for each of the 4 techniques. Results: In the axilla, the largest improvement for 3D-CRT compared to 2D-RT was for homogeneity index (13.9 vs. 54.3), at the expense of higher lung $V_{20}$ (28.0% vs. 12.6%). In the groin, the largest improvements for 3D-CRT compared to 2D-RT were for anorectum $D_{max}$ (13.6 vs. 38.9 Gy), bowel $D_{200cc}$ (7.3 vs. 23.1 Gy), femur $D_{50}$ (34.6 vs. 57.2 Gy), and genitalia $D_{max}$ (37.6 vs. 51.1 Gy). IMRT had further improvements compared to 3D-CRT for humerus $D_{mean}$ (16.9 vs. 22.4 Gy), brachial plexus $D_5$ (57.4 vs. 61.3 Gy), bladder $D_5$ (26.8 vs. 36.5 Gy), and femur $D_{50}$ (18.7 vs. 34.6 Gy). Fewer differences were observed between IMRT and VMAT. Conclusion: Compared to 2D-RT and 3D-CRT, IMRT and VMAT had dosimetric advantages in the treatment of nodal regions of skin cancer patients.

Synthesis and Evaluation of a Ligand Targeting the Somatostatin Receptor for Drug Delivery to Tumor Cell (암세포 내로의 약물 전달 증진 목적의 신규 소마토스타틴 수용체 타겟리간드 합성 및 평가)

  • Choi, SunJu;Hong, YoungDon;Lee, SoYoung;Jung, SungHee
    • Journal of Radiation Industry
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    • v.9 no.4
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    • pp.193-198
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    • 2015
  • Most of targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells to produce its cytotoxic effect. Either small molecule drugs or monoclonal antibodies are mostly used in targeted therapies. Unfortunately, targeted therapy has a certain degree of unwanted side effect like other cytotoxicity inducing chemotherapies. To overcome and to reduce unwanted side effects during a cancer therapy, recently radiopeptide therapies has got the worlds' attraction for the tumor targeting modalities due to its beneficial effect on less side effect compared to cytotoxic chemotherapies. Among radiopeptide therapies, $^{177}Lu$-DOTATATE is a major modality as an effective one invented so far in treating neuroendocrine tumor (NET) and it has been in clinical trials at least one decade. Although it does have rather effective therapeutic effect on NET, it has less effective in rather large solid tumor. There are many ways to improve or increase therapeutic effect of radiopeptide are a finding the potent small molecules to target the tumor site selectively, or a labeling with radioisotope of emitting high energy, or an improving its biological half-life by introducing different moieties to increase lipophilicity. Present study was focus to increase a biological half-life of radio somatostatin which will target the somatostatin receptor by altering the bifunctional chelator (BFCA) by introducing lipophilic moiety to the somatostatin, which would make the labeled peptide stay longer in the tumor site and thus it can intensify the therapeutic effect on tumor cell itself and around tissues.

Sonoporation with echogenic liposome: therapeutic effect on a breast cancer cell (약물이 탑재된 미소기포와 결합된 sonoporation: 유방암세포에 대한 치료효과)

  • Park, Juhyun;Lee, Hana;Lee, Yougyeong;Seo, Jongbum
    • The Journal of the Acoustical Society of Korea
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    • v.41 no.5
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    • pp.501-506
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    • 2022
  • Echogenic liposome contains both liquid and gas inside the shell. In ultrasound mediated drug delivery, sonoporation, these new microbubbles can be an attractive drug carrier since they can be loaded water soluble drugs and drug molecules can be unloaded at the specific location with ultrasound sonication. In this paper, the structure of the echogenic liposome was confirmed with EF-TEM and the positive effect of sonoporation with echogenic liposome was comparatively evaluated on MDA-MB-231 cells which is a type of breast cancer cell with Doxorubicin. Control group (Group 1), Doxorubicin only (Group 2), sonoporation with Doxorubicin and hollow microbubbles (Group 3), sonoporation with Doxorubicin loaded echogenic liposome (Group 4) were classified and experiments were conducted. According to the results, Group 4 is at least 1.4 times better in inducing necrosis of cancer cells. Therefore, we conclude echogenic liposome could be one of the most useful form of microbubbles in sonoporation.

Preclinical Study on Biodistribution of Mesenchymal Stem Cells after Local Transplantation into the Brain

  • Narayan Bashyal;Min Gyeong Kim;Jin-Hwa Jung;Rakshya Acharya;Young Jun Lee;Woo Sup Hwang;Jung-Mi Choi;Da-Young Chang;Sung-Soo Kim;Haeyoung Suh-Kim
    • International Journal of Stem Cells
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    • v.16 no.4
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    • pp.415-424
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    • 2023
  • Therapeutic efficacy of mesenchymal stem cells (MSCs) is determined by biodistribution and engraftment in vivo. Compared to intravenous infusion, biodistribution of locally transplanted MSCs are partially understood. Here, we performed a pharmacokinetics (PK) study of MSCs after local transplantation. We grafted human MSCs into the brains of immune-compromised nude mice. Then we extracted genomic DNA from brains, lungs, and livers after transplantation over a month. Using quantitative polymerase chain reaction with human Alu-specific primers, we analyzed biodistribution of the transplanted cells. To evaluate the role of residual immune response in the brain, MSCs expressing a cytosine deaminase (MSCs/CD) were used to ablate resident immune cells at the injection site. The majority of the Alu signals mostly remained at the injection site and decreased over a week, finally becoming undetectable after one month. Negligible signals were transiently detected in the lung and liver during the first week. Suppression of Iba1-positive microglia in the vicinity of the injection site using MSCs/CD prolonged the presence of the Alu signals. After local transplantation in xenograft animal models, human MSCs remain predominantly near the injection site for limited time without disseminating to other organs. Transplantation of human MSCs can locally elicit an immune response in immune compromised animals, and suppressing resident immune cells can prolong the presence of transplanted cells. Our study provides valuable insights into the in vivo fate of locally transplanted stem cells and a local delivery is effective to achieve desired dosages for neurological diseases.