Delivery of Cancer Therapeutics Using Nanotechnology

Nanoparticles have been investigated as drug carriers, because they provide a great opportunity due to their advantageous features: (i) various formulations using organic/inorganic materials, (ii) easy modification of targeting molecules, drugs or other molecules on them, (iii) effective delivery to target sites, resulting in high therapeutic efficacy and (iv) controlling drug release by external/internal stimuli. Because of these features, therapeutic efficacy can be improved and unwanted side effects can be reduced. Theranostic nanoparticles have been developed by incorporating imaging agents in drug carriers as all-in-one system, which makes it possible to diagnose and treat cancer by monitoring drug delivery behavior simultaneously. Recently, stimuli-responsive, activatable nanomaterials are being applied that are capable of producing chemical or physical changes by external stimuli. By using these nanoparticles, multiple tasks can be carried out simultaneously, e.g., early and accurate diagnosis, efficient cataloguing of patient groups of personalized therapy and real-time monitoring of disease progress. In this paper, we describe various types of nanoparticles for drug delivery systems, as well as theranostic systems.ope

Double-ligand modulation for engineering magnetic nanoclusters

Magnetic nanoclusters (MNCs) are agglomerated individual magnetic nanoparticles (MNPs) that show great promise in increasing magnetic resonance imaging (MRI) sensitivity. Here, we report an effective strategy to engineer MNCs based on double-ligand modulation to enhance MRI sensitivity. The oleic acid-coated individual MNPs self-assembled and then were enveloped by polysorbate 80, using a nanoemulsion method to prepare MNCs. By modulating the amounts of the two ligands, and thus the size and magnetic content of the resultant MNCs, we were able to enormously improve MRI sensitivity.ope

Efficient CD44-targeted magnetic resonance imaging (MRI) of breast cancer cells using hyaluronic acid (HA)-modified MnFe2O4 nanocrystals

Targeted molecular imaging with hyaluronic acid (HA) has been highlighted in the diagnosis and treatment of CD44-overexpressing cancer. CD44, a receptor for HA, is closely related to the growth of cancer including proliferation, metastasis, invasion, and angiogenesis. For the efficient detection of CD44, we fabricated a few kinds of HA-modified MnFe2O4 nanocrystals (MNCs) to serve as specific magnetic resonance (MR) contrast agents (HA-MRCAs) and compared physicochemical properties, biocompatibility, and the CD44 targeting efficiency. Hydrophobic MNCs were efficiently phase-transferred using aminated polysorbate 80 (P80) synthesized by introducing spermine molecules on the hydroxyl groups of P80. Subsequently, a few kinds of HA-MRCAs were fabricated, conjugating different ratios of HA on the equal amount of phase-transferred MNCs. The optimized conjugation ratio of HA against magnetic content was identified to exhibit not only effective CD44 finding ability but also high cell viability through in vitro experiments. The results of this study demonstrate that the suggested HA-MRCA shows strong potential to be used for accurate tumor diagnosis.ope

Chitosan-based intelligent theragnosis nanocomposites enable pH-sensitive drug release with MR-guided imaging for cancer therapy

Smart drug delivery systems that are triggered by environmental conditions have been developed to enhance cancer therapeutic efficacy while limiting unwanted effects. Because cancer exhibits abnormally high local acidities compared to normal tissues (pH 7.4) due to Warburg effects, pH-sensitive systems have been researched for effective cancer therapy. Chitosan-based intelligent theragnosis nanocomposites, N-naphthyl-O-dimethymaleoyl chitosan-based drug-loaded magnetic nanoparticles (NChitosan-DMNPs), were developed in this study. NChitosan-DMNPs are capable of pH-sensitive drug release with MR-guided images because doxorubicin (DOX) and magnetic nanocrystals (MNCs) are encapsulated into the designed N-naphthyl-O-dimethymaleoyl chitosan (N-nap-O-MalCS). This system exhibits rapid DOX release as acidity increases, high stability under high pH conditions, and sufficient capacity for diagnosing and monitoring therapeutic responses. These results demonstrate that NChitosan-DMNPs have potential as theragnosis nanocomposites for effective cancer therapy.ope

One-pot synthesis of magnetic nanoclusters enabling atherosclerosis-targeted magnetic resonance imaging

In this study, dextran-encrusted magnetic nanoclusters (DMNCs) were synthesized using a one-pot solution phase method for detection of atherosclerosis by magnetic resonance imaging. Pyrenyl dextran was used as a surfactant because of its electron-stabilizing effect and its amphiphilic nature, rendering the DMNCs stable and water-dispersible. The DMNCs were 65.6±4.3 nm, had a narrow size distribution, and were superparamagnetic with a high magnetization value of 60.1 emu/g. Further, they showed biocompatibility and high cellular uptake efficiency, as indicated by a strong interaction between dextran and macrophages. In vivo magnetic resonance imaging demonstrated the ability of DMNCs to act as an efficient magnetic resonance imaging contrast agent capable of targeted detection of atherosclerosis. In view of these findings, it is concluded that DMNCs can be used as magnetic resonance imaging contrast agents to detect inflammatory disease.ope

심혈관계 질환 가족에서 혈중 지질농도와 Apo AI-CIII-AIV cluster와의 연관분석.

Brain Korea 21 Project for Medical Sciences/석사[한글] 심혈관계 질환은 여러 요인들에 의해 발생되는 다 인자성 질환이다. 최근 유전체 관련 연구가 활성화되면서 심혈관계 질환 및 그 위험요인과 유전형과의 관련성에 대해 활발한 연구가 진행되어오고 있으나 혈중지질대사에 관여하는 유전자들의 분리모형 및 관련성에 대한 연구는 그 결과들이 아직 논란이 많은 실정이다. 본 연구에서는 심혈관계 질환자들과 그 가족을 중심으로 혈중지질 치에 대한 분리모형을 설정하고 혈중 지질 치와 관련이 있다고 알려져 있는 Apo AI-CIII-AIV 유전자 근접한 유전체 부위에 대해 microsatellite marker를 이용한 연관분석을 시행하였다. 심혈관계질환으로 진단 받은 환자와 그 가족 (93가족, 701구성원)을 대상으로 저밀도 지단백 콜레스테롤에 대한 분리분석결과 codominant Mendelian 모형과 equal transmission 모형을 따랐다. 고밀도 지단백 콜레스테롤에 대한 분리분석에서는 dominant Mendelian 모형이 우세하게 나타났다. 대상가족 중 다세대이며 가족구성원이 많은 가족 30 가족을 선정하여 이를 대상으로 연관분석을 시행한 결과 HDL-콜레스테롤에 대한 분석에서는 모든 marker에서 연관성이 없었으며 LDL-콜레스테롤에 대한 분석에서는 marker들 중 D11S912 (130.9cM)에서 비교적 높은 관련성을 나타냈으나 유의성은 가지지 못하였다 (LOD score =1.18, p=0.099). 분석된 30가족 중 codominant Mendelian 모형을 따르는 21 가족을 대상으로 연관분석을 시행한 결과에서는 유의성은 비교적 높아졌으나 LOD score의 유의한 차이는 없었다(LOD score =1.06, p=0.014). 이상의 결과로 심혈관계 질환 가족에서 LDL-콜레스테롤에 대한 분리모형은 codominant Mendelian 및 equal transmission 모형을 따르고 HDL-콜레스테롤에 대한 분리모형은 dominant Mendelian 모형을 우세하게 따르는 것을 알 수 있었다. 또한 Apo AI-CIII-AIV 유전자 근접 부위에서 LDL-콜레스테롤 농도에 영향을 주는 유전자가 있을 가능성을 시사하며 이들 유전자에 대한 연구에 이용될 수 있을 것이다. -------------------- 핵심 되는 말 : 유전자 분리분석, 연관분석, 혈중 콜레스테롤, 심혈관계 질환, Apo AI-CIII-AIV 유전자 [영문] Background Cardiovascular disease (CVD) is a complex disorder, which the genetic contributions have significant roles with environmental factors. In the many studies, increased plasma lipid levels except HDL-cholesterol were directly correlated with cardiovascular risk. The aim of this study was to determine whether Apo AI-CIII-AIV gene cluster region (chromosome 11q23) contains specific loci that affect plasma lipid concentration or not. Methods and Results The 701 individuals from 93 CVD families were recruited. We collected genealogical informations for all participants and measured plasma lipid levels. Segregation analysis showed that the LDL-cholesterol follows the codominant Mendelian model with 61.2% of the variation and the equal transmission model. For HDL-cholesterol, the segregation analysis showed a dominant Mendelian model accounted for 51.8% of the variation. For linkage analysis, we selected 30 families (305 individuals) those have a relatively large number of subjects and multi-generation comparatively. In the analysis for the HDL-cholesterol, none of genetic markers at Apo AI-CIII-AIV gene cluster showed LOD score as evidence of linkage. In the analysis for the LDL-cholesterol, the highest LOD score was found at D11S912 of 130.9 cM (LOD score =1.18, p=0.099). To confirm the linkage between a putative gene that affects LDL-cholesterol level and D11S912, we reanalyzed the linkage with 21 families that favored a codominant Mendelian model, but there was no significant difference in LOD score. Conclusion The segregation analysis showed both LDL-cholesterol and HDL-cholesterol are under the genetic influences, following the Mendelian model. However, HDL-cholesterol showed no linkage to the Apo AI-CIII-AIV gene cluster, indicating the major gene effect influence in HDL-cholesterol is not explained by these loci. For LDL-cholesterol, we found the tentative linked loci at 11q23.ope

중금속 비소의 대사체 (Monomethylarsonous Acid; MMAⅢ)에 의한 혈관의 기능 손상

학위논문(석사)--서울대학교 대학원 :약학과 위생약학전공,2006.Maste

Determination of magnetic helicity of a solar active region using the linear force-free field model

Thesis(master`s)--서울대학교 대학원 :지구환경과학부 천문학전공,2006.Maste

Self-fabricated dextran-coated gold nanoparticles using pyrenyl dextran as a reducible stabilizer and their application as CT imaging agents for atherosclerosis agents for atherosclerosis

Self-fabricated dextran-coated gold nanoparticles using pyrenyl dextran as a reducible stabilizer and their application as CT imaging agents for atherosclerosisope

Effect of Ligand Structure on MnO Nanoparticles for Enhanced T1 Magnetic Resonance Imaging of Inflammatory Macrophages

Carboxymethyl-dextran (CM-dextran) replaced the hydrophobic oleylamine ligands on the surfaces of MnO nanoparticles, rendering them highly water-soluble by allowing direct contact with excited water protons. Solution MRI studies of the two types of nanoparticles, exchanged and bilayered, with different core sizes have shown that the exchanged ligand structure exhibits significantly enhanced longitudinal relaxation. The modification with dextran converted the nanoparticles into effective T1 MRI contrast agents, as well as promoting strong interactions with macrophages. Thus, it is a potential MR contrast agent for visualizing inflammatory macrophages.ope