다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

1. Introduction 20642. Synthesis of Magnetic Nanoparticles 20662.1. Classical Synthesis by Coprecipitation 20662.2. Reactions in Constrained Environments 20682.3. Hydrothermal and High-TemperatureReactions20692.4. Sol-Gel Reactions 20702.5. Polyol Methods 20712.6. Flow Injection Syntheses 20712.7. Electrochemical Methods 20712.8. Aerosol/Vapor Methods 20712.9. Sonolysis 20723. Stabilization of Magnetic Particles 20723.1. Monomeric Stabilizers 20723.1.1. Carboxylates 20733.1.2. Phosphates 20733.2. Inorganic Materials 20733.2.1. Silica 20733.2.2. Gold 20743.3. Polymer Stabilizers 20743.3.1. Dextran 20743.3.2. Polyethylene Glycol (PEG) 20753.3.3. Polyvinyl Alcohol (PVA) 20753.3.4. Alginate 20753.3.5. Chitosan 20753.3.6. Other Polymers 20753.4. Other Strategies for Stabilization 20764. Methods of Vectorization of the Particles 20765. Structural and Physicochemical Characterization 20785.1. Size, Polydispersity, Shape, and SurfaceCharacterization20795.2. Structure of Ferro- or FerrimagneticNanoparticles20805.2.1. Ferro- and Ferrimagnetic Nanoparticles 20805.3. Use of Nanoparticles as Contrast Agents forMRI20825.3.1. High Anisotropy Model 20845.3.2. Small Crystal and Low Anisotropy EnergyLimit20855.3.3. Practical Interests of Magnetic NuclearRelaxation for the Characterization ofSuperparamagnetic Colloid20855.3.4. Relaxation of Agglomerated Systems 20856. Applications 20866.1. MRI: Cellular Labeling, Molecular Imaging(Inﬂammation, Apoptose, etc.)20866.2.

Magnetic Iron Oxide Nanoparticles: Synthesis, Stabilization, Vectorization, Physicochemical Characterizations, and Biological Applications

We investigated the intracellular uptake of different sized and shaped colloidal gold nanoparticles. We showed that kinetics and saturation concentrations are highly dependent upon the physical dimensions of the nanoparticles (e.g., uptake half-life of 14, 50, and 74 nm nanoparticles is 2.10, 1.90, and 2.24 h, respectively). The findings from this study will have implications in the chemical design of nanostructures for biomedical applications (e.g., tuning intracellular delivery rates and amounts by nanoscale dimensions and engineering complex, multifunctional nanostructures for imaging and therapeutics).

Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells.

Nanotechnology is a multidisciplinary field, which covers a vast and diverse array of devices derived from engineering, biology, physics and chemistry. These devices include nanovectors for the targeted delivery of anticancer drugs and imaging contrast agents. Nanowires and nanocantilever arrays are among the leading approaches under development for the early detection of precancerous and malignant lesions from biological fluids. These and other nanodevices can provide essential breakthroughs in the fight against cancer.

Cancer nanotechnology: opportunities and challenges.

Magnetic Nanoparticles in MR Imaging and Drug Delivery

A multifunctional nanoprobe capable of targeting glioma cells, detectable by both magnetic resonance imaging and fluorescence microscopy, was developed. The nanoprobe was synthesized by coating iron oxide nanoparticles with covalently bound bifunctional poly(ethylene glycol) (PEG) polymer, which were subsequently functionalized with chlorotoxin and the near-infrared fluorescing molecule Cy5.5. Both MR imaging and fluorescence microscopy showed significant preferential uptake of the nanoparticle conjugates by glioma cells. Such a nanoprobe could potentially be used to image resections of glioma brain tumors in real time and to correlate preoperative diagnostic images with intraoperative pathology at cellular-level resolution.

Optical and MRI Multifunctional Nanoprobe for Targeting Gliomas

A magnetic nanoparticle conjugate was developed that can potentially serve both as a contrast enhancement agent in magnetic resonance imaging and as a drug carrier in controlled drug delivery, targeted at cancer diagnostics and therapeutics. The conjugate is made of iron oxide nanoparticles covalently bound with methotrexate (MTX), a chemotherapeutic drug that can target many cancer cells whose surfaces are overexpressed by folate receptors. The nanoparticles were first surface-modified with (3-aminopropyl)trimethoxysilane to form a self-assembled monolayer and subsequently conjugated with MTX through amidation between the carboxylic acid end groups on MTX and the amine groups on the particle surface. Drug release experiments demonstrated that MTX was cleaved from the nanoparticles under low pH conditions mimicking the intracellular conditions in the lysosome. Cellular viability studies in human breast cancer cells (MCF-7) and human cervical cancer cells (HeLa) further demonstrated the effectiveness of such chemical cleavage of MTX inside the target cells through the action of intracellular enzymes. The intracellular trafficking model proposed was supported through nanoparticle uptake studies which demonstrated that cells expressing the human folate receptor internalized a higher level of nanoparticles than negative control cells.

Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells.

We report the development of a biostable methotrexate-immobilized iron oxide nanoparticle drug carrier that may potentially be used for real-time monitoring of drug delivery through magnetic resonance imaging. Methotrexate (MTX) was immobilized on the nanoparticle surface via a poly(ethylene glycol) self-assembled monolayer (PEG SAM). The cytotoxicity of the nanoparticle-drug conjugate (NP-PEG-MTX) to target cells was studied with 9L glioma cells. Cellular uptake experiments showed that the uptake of NP-PEG-MTX conjugates by glioma cells was considerably higher than that of control nanoparticles. Magnetic resonance imaging in 9L cells cultured with NP-PEG-MTX of various concentrations showed significant contrast enhancement. NP-PEG-MTX demonstrated higher cytotoxicity in 9L cells to free MTX in vitro. Leucovorin, an MTX antidote, was used to rescue the cells that had been exposed to NP-PEG-MTX or free MTX, and the experiment verified the biocompatibility of NP-PEG-MTX conjugates and the MTX on NP-PEG-MTX conjugates to be the true source of the cytotoxicity to the target cells. TEM results showed that NP-PEG-MTX conjugates were internalized into the 9L cellular cytoplasm and retained its crystal structure therein for up to 144 h, as identified by electron diffraction. This prolonged particle retention may allow physicians to image tumor cells exposed to the NP-PEG-MTX conjugate over an extended therapeutic time course.

Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery.

We report the development and in vitro study of a nanoconjugate serving as a targeted magnetic resonance imaging (MRI) contrast enhancement agent for detection of cancer cells overexpressing the folate receptor. The nanoconjugate was synthesized by coating superparamagnetic iron oxide nanoparticles with covalently bound bifunctional poly(ethylene glycol) (PEG), followed by conjugation with folic acid (FA). The specificity of the nanoconjugate targeting cancerous cells was demonstrated by comparative intracellular uptake of the nanoconjugate and PEG-/dextran-coated nanoparticles by human adenocarcinoma HeLa cells. Preferential targeting to cancerous cells was studied by comparing the uptake of the nanoconjugate by HeLa cells and by non-FR expressing osteosarcoma MG-63 cells. Uptake of the nanoconjugate by HeLa cells after 4 h incubation was found to be a 12-fold higher than that of PEG- or dextran-coated nanoparticles as quantified by inductively coupled plasma spectroscopy. A significant negative contrast enhancement was observed with magnetic resonance (MR) phantom imaging for HeLa cells over MG-63 cells, when both were cultured with the nanoconjugate. Specificity of the nanoconjugate for folate receptors was also verified with a competitive inhibition assay, in which HeLa cells were incubated with both NP-PEG-FA and free FA. The bifunctional PEG used has amide linkages within the PEG chains that can form interchain hydrogen bonding, leading to improved stability of the PEG coating. Self-assembled PEG can be controlled at the molecular level and are suitable for nanoscale coatings.

Conroy Sun

Papers

Magnetic Nanoparticles in MR Imaging and Drug Delivery

Optical and MRI Multifunctional Nanoprobe for Targeting Gliomas

Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells.

Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery.

Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI.