Construction of double targeting system

双目标体系构建

• 批准号: 10145104
• 负责人: KOBAYASHI Takeshi
• 金额: $ 83.33万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas (A)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10145104/
• 关键词: double targeting; Hypertbermia; Magnetic particles; Thermo-responsive polymeric micelles; Scanning chemiluminescence microscopy I; Receptor-mediated gene transfer system; Protamine-modified lipid; Plant cell separation; 時間的ターゲティング; 空間的ターゲティング; ミ

In cell surface, many recepter proteins are presented and the specific biomolecules are recognized by these recepter proteins. These mechanisms can be analyzed from chemical view points. To systemize the biotergeting, the double targeting system for biomolecules was investigated. Dr. Kobayashi has been studying the hyperthermia treatment for cancer therapy by using magnetic particles and subsequent high frequency magnetic field irradiation. In this system, it is important to improve the distribution of magnetic particles (the spatial targeting) and to treat at I best timing (the timing targeting). Therefore, the development of magnetic particles with double targeting ability was development, which was conjugated with antibodies. Using the particles, hyperthermia of kidney cancer was performed and complete regression of cancer reached more than 79%. Dr. Okano studied thermo-responsive polymeric micelles with the core-shell structure for selective anticancer drug release at solid tumor s … More ites upon local heating. Polymeric micelles were formed from block copolymers with a thermo-responsive poly(N-isopropylacrylamide) chain and a hydrophobic drug-incorporating polymer chain. Dr. Matsue developed scanning electrochemical microscopy (SECM) and scanning chemiluminescence microscopy (SCLM) for imaging localized enzymes such as horse radish peroxidase (HRP) immobilized at a glass substrate. Both systems with microelectrode tip gave clear images indicating the activity of an immobilized enzyme. It was found that using imaged antibody chips with the SECM/SCLM system, leukocidin, a highly toxic protein, can be detected in pg/ml range. Dr. Iijima studied receptor-mediated gene transfer system by modifying with a ligand such as insulin and galactose residues in order to improve the efficiency and specificity of the gene delivery. By using these lipid vesicle, the transfection efficiency was increased 3-4-fold. Dr. Seki tried to evaluate the plant cell heterogeneity and to biotarget the high-producing cells in the heterogeneous populations for the development of a novel cell sepiaration method, such as an image processing system, an affinity adsorption system, and an aqueous two-phase system in a microchannel. Less

在细胞表面存在许多受体蛋白，并且这些受体蛋白可以识别特定的生物分子。为了使生物靶向系统化，小林博士对生物分子的双重靶向系统进行了研究。通过使用磁性粒子和随后的高频磁场照射进行癌症治疗的热疗在该系统中，重要的是改善磁性粒子的分布（空间靶向）并在最佳时机（时机）进行治疗。因此，冈野博士研究了具有双重靶向能力的磁性粒子的开发，该粒子与抗体结合，进行了肾癌的热疗，并且癌症的完全消退达到了79％以上。具有核壳结构的响应性聚合物胶束，可在局部加热时在实体瘤中选择性释放抗癌药物。聚合物胶束由具有热响应性的嵌段共聚物形成。 Matsue 博士开发了扫描电化学显微镜 (SECM) 和扫描化学发光显微镜 (SCLM)，用于对固定在玻璃基板上的辣根过氧化物酶 (HRP) 等局部酶进行成像。两个系统都通过微电极尖端提供清晰的图像，表明固定化酶的活性。发现使用成像抗体芯片。 SECM/SCLM系统，杀白细胞素是一种高毒性蛋白质，可以在pg/ml范围内检测到。Iijima博士通过用胰岛素和半乳糖残基等配体进行修饰，研究了受体介导的基因转移系统，以提高效率和特异性。通过使用这些脂质囊泡，转染效率提高了 3-4 倍，Seki 博士尝试评估植物细胞的异质性并生物靶向异质中的高产细胞。开发新型细胞分离方法的群体，例如图像处理系统、亲和吸附系统和微通道中的水两相系统。

项目成果

Masashige Shinkaiほか: "Intracelluar hyperthermia for cancer using magnetic cationic liposomes"Journal of Magnetism and Magnetic Materials. 194・1. 176-184 (1999)

Masashige Shinkai等：“使用磁性阳离子脂质体治疗癌症”Journal of Magnetism and Magnetic Materials 194・1（1999）。

J.E.Chung: "Effect of molecular architecture of hydrophobically moditied poly (N-isopropylacrylamide)on the formation of thermoresponsive core-shell micellan drug carrier" J.Controlled Release. 53・2. 119-130 (1998)

J.E.Chung：“疏水改性聚（N-异丙基丙烯酰胺）的分子结构对热响应性核壳胶束药物载体形成的影响”J.Controlled Release 53・2（1998）。

M.Nakamura: "Enhanced anthocyanin methylation by growth limitation in strawberry suspension culture" Enz.Microb.Technol.22・4. 404-408 (1998)

M.Nakamura：“草莓悬浮培养中通过生长限制增强花青素甲基化”Enz.Microb.Technol.22·404-408（1998）。

S.Mizuarai 他: "Protamine-modified DDAB lipid vesicles promote gene transfer in the presence of serum"Journal of Biochemistry. 129. 125-132 (2001)

S. Mizuarai 等人：“鱼精蛋白修饰的 DDAB 脂质囊泡在血清存在下促进基因转移”《生物化学杂志》129. 125-132 (2001)。

B.Le 他: "Preparation of tumor-specific magnetoliposomes and their application for hyperthermia"J.Chem.Eng.Jpn. 34. 66-72 (2001)

B.Le等：“肿瘤特异性磁脂质体的制备及其在热疗中的应用”J.Chem.Eng.Jpn.34.66-72(2001)