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        Nanoparticle-Based Combination Therapy for Cancer Treatment.

        Yhee, Ji Young,Son, Sejin,Lee, Hyukjin,Kim, Kwangmeyung Bentham Science Publishers 2015 CURRENT PHARMACEUTICAL DESIGN Vol.21 No.22

        <P>In recent years, combination of different types of therapies using nanoparticles has emerged as an advanced strategy for cancer treatment. Most of all, combination of chemotherapeutic drug and siRNA in nanoformulation has shown a great potential, because siRNA-mediated specific gene silencing can compensate for the incomplete anti-cancer actions of chemotherapy. In this article, nanoparticle-based combination therapy for cancer treatment is introduced to be focused on the therapeutic chemical and siRNA combination. It is classified into 3 groups: 1) general chemotherapy combined with siRNA carrying nanoparticle, 2) co-delivery of chemical and siRNA therapeutics within a single nanoparticle, and 3) Use of multiple nanoparticles for chemical and siRNA therapeutics. The purpose of the combination and the mechanisms of anti-cancer action was described according to the categories. Examples of some recent developments of nanotechnology-based chemo- and siRNA- therapeutics combination therapy are summarized for better understanding of its practical application.</P>

      • SCISCIESCOPUS

        Self-assembled glycol chitosan nanoparticles for disease-specific theranostics

        Yhee, J.Y.,Son, S.,Kim, S.H.,Park, K.,Choi, K.,Kwon, I.C. Elsevier Science Publishers 2014 Journal of controlled release Vol.193 No.-

        Hydrophobically modified glycol chitosan (hGC) conjugates spontaneously form self-assembled nanoparticles (NPs) in aqueous conditions, and glycol chitosan NPs (CNPs) have been extensively studied for the past few decades. For disease-specific theranostics, CNPs could be simply modified with imaging agents, and the hydrophobic domains of hGC are available for encapsulation of various drugs. Based on the excellent physiochemical and biological properties, CNPs have been investigated for multimodal imaging and target specific drug delivery. In particular, a recent application of CNPs has shown great potential as an efficient theranostic system because the CNPs could be utilized for a disease-specific theranostic delivery system of different imaging agents and therapeutics, simultaneously. Furthermore, various therapeutic agents including chemo-drugs, nucleotides, peptides, and photodynamic chemicals could be simply encapsulated into the CNPs through hydrophobic or charge-charge interactions. Under in vivo conditions, the encapsulated imaging agents and therapeutic drugs have been successfully delivered to targeted diseases. In this article, the overall research progress on CNPs is reviewed from early works. The current challenges of CNPs to overcome in theranostics are also discussed, and continuous studies would provide more opportunities for early diagnosis of diseases and personalized medicine.

      • Tumor-Targeting Transferrin Nanoparticles for Systemic Polymerized siRNA Delivery in Tumor-Bearing Mice

        Yhee, Ji Young,Lee, So Jin,Lee, Sangmin,Song, Seungyong,Min, Hyun Su,Kang, Sun-Woong,Son, Sejin,Jeong, Seo Young,Kwon, Ick Chan,Kim, Sun Hwa,Kim, Kwangmeyung American Chemical Society 2013 Bioconjugate chemistry Vol.24 No.11

        <P>Transferrin (TF) is widely used as a tumor-targeting ligand for the delivery of anticancer drugs because the TF receptor is overexpressed on the surface of various fast-growing cancer cells. In this article, we report on TF nanoparticles as an siRNA delivery carrier for in vivo tumor-specific gene silencing. To produce siRNA carrying TF nanoparticles (NPs), both TF and siRNA were chemically modified with sulfhydryl groups that can build up self-cross-linked siRNA-TF NPs. Self-polymerized 5′-end thiol-modified siRNA (poly siRNA, psi) and thiolated transferrin (tTF) were spontaneously cross-linked to form stable NPs (psi-tTF NPs) under optimized conditions, and they could be reversibly degraded to release functional monomeric siRNA molecules under reductive conditions. Receptor-mediated endocytosis of TF induced rapid tumor-cell-specific uptake of the psi-tTF NPs, and the internalized NPs resulted in a downregulation of the target protein in red-fluorescent-protein-expressing melanoma cancer cells (RFP/B16F10) with negligible cytotoxicity. After systemic administration, the psi-tTF NPs showed marked accumulation at the tumor, leading to successful target-gene silencing in vivo. This psi-tTF NP system provided a safe and effective strategy for in vivo systemic siRNA delivery for cancer therapy.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bcches/2013/bcches.2013.24.issue-11/bc400226b/production/images/medium/bc-2013-00226b_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bc400226b'>ACS Electronic Supporting Info</A></P>

      • Theranostic applications of organic nanoparticles for cancer treatment

        Yhee, Ji Young,Son, Sohee,Kim, Namho,Choi, Kuiwon,Kwon, Ick Chan Cambridge University Press (Materials Research Soc 2014 MRS bulletin Vol.39 No.3

        <▼1><B>Abstract</B><P/></▼1><▼2><P>Research in nanotechnology-based molecular imaging and targeted drug delivery has resulted in a noticeable progress in cancer theranosis, the simultaneous application of cancer therapy and diagnosis. Theranostic nanoparticles (NPs) have been developed using diverse base materials, and organic materials are of major interest in the synthesis and preparation of these NPs. A variety of organic NPs have their own advantages, depending on the physiochemical and biological properties of the base materials. This article reviews recent developments in organic NPs, which are grouped into four major kinds of base materials: lipids, polysaccharides, peptides/proteins, and synthetic polymers. The advantageous properties of frequently used base materials and practical performance of the various organic NPs <I>in vivo</I> are discussed. These theranostic NPs offer new opportunities for effective cancer treatment.</P></▼2>

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        Cancer-targeted MDR-1 siRNA delivery using self-cross-linked glycol chitosan nanoparticles to overcome drug resistance

        Yhee, J.Y.,Song, S.,Lee, S.J.,Park, S.G.,Kim, K.S.,Kim, M.G.,Son, S.,Koo, H.,Kwon, I.C.,Jeong, J.H.,Jeong, S.Y.,Kim, S.H.,Kim, K. Elsevier Science Publishers 2015 Journal of controlled release Vol.198 No.-

        P-glycoprotein (Pgp) mediated multi-drug resistance (MDR) is a major cause of failure in chemotherapy. In this study, small interfering RNA (siRNA) for Pgp down-regulation was delivered to tumors to overcome MDR in cancer. To achieve an efficient siRNA delivery in vivo, self-polymerized 5'-end thiol-modified siRNA (poly-siRNA) was incorporated in tumor targeting glycol chitosan nanoparticles. Pgp-targeted poly-siRNA (psi-Pgp) and thiolated glycol chitosan polymers (tGC) formed stable nanoparticles (psi-Pgp-tGC NPs), and the resulting nanoparticles protected siRNA molecules from enzymatic degradation. The psi-Pgp-tGC NPs could release functional siRNA molecules after cellular delivery, and they were able to facilitate siRNA delivery to Adriamycin-resistant breast cancer cells (MCF-7/ADR). After intravenous administration, the psi-Pgp-tGC NPs accumulated in MCF-7/ADR tumors and down-regulated P-gp expression to sensitize cancer cells. Consequently, chemo-siRNA combination therapy significantly inhibited tumor growth without systemic toxicity. These psi-Pgp-tGC NPs showed great potential as a supplementary therapeutic agent for drug-resistant cancer.

      • SCISCIESCOPUS

        Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles

        Yhee, Ji Young,Jeon, Sangmin,Yoon, Hong Yeol,Shim, Man Kyu,Ko, Hyewon,Min, Jiwoong,Na, Jin Hee,Chang, Hyeyoun,Han, Hyounkoo,Kim, Jong-Ho,Suh, Minah,Lee, Hyukjin,Park, Jae Hyung,Kim, Kwangmeyung,Kwon, Elsevier Science Publishers 2017 Journal of controlled release Vol.267 No.-

        <P><B>Abstract</B></P> <P>In cancer theranostics, the main strategy of nanoparticle-based targeted delivery system has been understood by enhanced permeability and retention (EPR) effect of macromolecules. Studies on diverse nanoparticles provide a better understanding of different EPR effects depending on their structure, physicochemical properties, and chemical modifications. Recently the tumor microenvironment has been considered as another important factor for determining tumor-targeted delivery of nanoparticles, but the correlation between EPR effects and tumor microenvironment has not yet been fully elucidated. Herein, ectopic subcutaneous tumor models presenting different tumor microenvironments were established by inoculation of SCC7, U87, HT29, PC3, and A549 cancer cell lines into athymic nude mice, respectively. In the five different types of tumor-bearing mice, tumor-targeted delivery of self-assembled glycol chitosan nanoparticles (CNPs) were comparatively evaluated to identify the correlation between the tumor microenvironments and targeted delivery of CNPs. As a result, neovascularization and extents of intratumoral extracellular matrix (ECM) were both important in determining the tumor targeted delivery of CNPs. The EPR effect was maximized in the tumors which include large extent of angiogenic blood vessels and low intratumoral ECM content. This comprehensive study provides substantial evidence that the EPR effects based tumor-targeted delivery of nanoparticles can be different depending on the tumor microenvironment in individual tumors. To overcome current limitations in clinical nanomedicine, the tumor microenvironment of the patients and EPR effects in clinical tumors should also be carefully studied.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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        지역사회의 생활 인프라 공급현황 분석 방법론

        이하연(Yhee, Hayeon),김성표(Kim, Sungpyo),강상혁(Kang, Sanghyeok) 대한토목학회 2021 대한토목학회논문집 Vol.41 No.3

        생활 인프라는 시민 삶의 질에 직접적인 영향을 미치는 국가 기반 시설로 누구에게나 균질한 서비스가 제공되어야 한다. 그러나 생활 인프라가 제공하는 서비스는 지역마다 차이를 보인다. 본 연구에서는 생활 인프라가 시민에게 제공하는 서비스의 정도를 정량적으로 평가하기 위하여 ‘접근성’과 ‘용량’의 평가요소로 구성된 생활 인프라 공급현황 분석방법을 제시하였다. 접근성은 거주지로부터 생활 인프라 시설까지의 소요시간을 기준으로 평가된다. 시설 사용에 있어 시민의 편리성을 나타내는 지표이다. 용량은 지역의 인구 대비 공급된 면적으로 평가된다. 그 지역에 시설이 충분히 제공되어 있는가를 평가하는 것이다. 연수구 행정동을 기준으로 하여 제시된 방법을 적용하고, 방법의 적용성을 논의하였다. 본 연구에서 제시하는 생활 인프라 공급현황 분석방법은 각 지역의 생활 인프라 공급계획 및 도시계획의 기초자료로 활용될 수 있을 것으로 사료된다. Community infrastructure contains national facilities that directly affect the quality of life of citizens. They need to be evenly supplied to every one of citizens. However, the services provided by infrastructure differ by region. In this paper, we propose a method to analyze the current status of the supply of community infrastructure consisting of accessibility and capacity. Accessibility can be evaluated by the time between residence blocks and facilities, which is an indicator of the convenience of citizens. Capacity is assessed by the area supplied for the local population, to assess whether facilities are being sufficiently supplied to the region. The method presented in this paper was applied on a case region to test the applicability. The analysis method of the supply status of community infrastructure in this study is considered to be used as a basic framework for regional supply plan of community infrastructure and urban planning.

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