Target cell specific delivery system of anti-cancer drugs by Bio-nano particles.

生物纳米颗粒抗癌药物的靶细胞特异性递送系统。

• 批准号: 15500317
• 负责人: TADA Hiroko
• 金额: $ 1.92万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15500317/
• 关键词: Drug delivery system; Molecular targetting; Artificial virus; anti-cancer drug; Protein Engineering; タンパク質工学

(1)To show that the hollow nanoparticle composed of the envelope protein of hepatitis B virus (Bio-nano particle) is an efficient delivery vector of pharmaceutical drugs to human liver, a model fluorescent compound (calcein) was enclosed in Bio-nanoparticles and added to the cultures of various cell lines. After 1-day culture, calcein was detected specifically in human hepatoma cells (HepG2) but not in cells derived from other tissues.(2)The system for measuring the amount of drugs encapsulated in Bio-nanoparticles was established by using calcein as a model, and used to find the optimum conditions of electroporation for encapsulation of calcein.(3)A mutant bio-nanoparticle with substitutions of 8 cysteine residues (M8 particle) was constructed to increase the efficiency of drug-encapsulation, since these cysteine residues frequently formed false and undesirable intramolecular disulfide bridges that prevent the drug influx into the particles. The amount of calcein encapsulated into the resultant M8 particle was 2.5-fold more than that into wild-type Bio-nanoparticle.(4)By using the conditions determined in (2), an anti-cancer drug of pacritaxel was encapsulated into the improved version of Bio-nanoparticle (M8 particle) described in (3) and added to the cultures of various cell lines. The anti-cancer drug encapsulated in Bio-nanoiparticles inhibited the growth of HepG2 cells 5-times more efficiently than the drug itself.Thus, these results showed the usefulness of Bio-nanoparticle as a delivery vector specific to human liver for pharmaceutical drugs.

（1）为表明，由乙型肝炎病毒的包膜蛋白（生物纳米颗粒）组成的空心纳米颗粒是对人肝脏的有效递送载体，模型荧光化合物（钙调蛋白）被封闭在生物纳米颗粒中，并添加到各种细胞系的培养物中。 1天培养后，在人肝癌细胞（HEPG2）中特异性检测到小结核素，但在来自其他组织的细胞中未检测到。构建了残基（M8颗粒）以提高药物封存的效率，因为这些半胱氨酸残基经常形成虚假和不良分子内二硫键，以防止药物涌入颗粒。封装在生成的M8颗粒中的小钙化量的量比野生型生物 - 纳米颗粒多2.5倍。（4）通过使用（2）中确定的条件，将pacritaxel的抗癌药封装在改进的生物 - 纳米粒子（M8粒子）的改进版本中（3）中所述的（3）和各种细胞中所述的培养基。封装在生物纳米粒子中的抗癌药物比药物本身更有效地抑制了HEPG2细胞的生长。

项目成果

中空バイオナノ粒子を用いたピンポイントドラッグデリバリーシステム

使用空心生物纳米颗粒的精确药物输送系统

• 发表时间: 2004
• 期刊: 高分子論文集 61(12)
• 作者: T.Matsumoto;et al.;Junichiro Futami;Junichiro Futami;Tadanori Yamada;Lei Li;Shin-ichi Miyoshi;Hiroko Tada;Takeshi Ogata;Luigi Strizzi;Oleg Gusev;山田 忠範
• 通讯作者: 山田 忠範

Activin A and betacellulin : effect on regeneration of pancreatic beta-cells in neonatal streptozotocin-treated rats.

激活素 A 和 betacellulin：对链脲佐菌素治疗的新生大鼠胰腺 β 细胞再生的影响。

• 发表时间: 2004
• 期刊: Diabetes. 53(3)
• 作者: T.Matsumoto;et al.;Junichiro Futami;Junichiro Futami;Tadanori Yamada;Lei Li
• 通讯作者: Lei Li

Insertional-fusion of basic fibroblast growth factor endowed ribonuclease 1 with enhanced cytotoxicity by steric blockade of inhibitor interaction.

碱性成纤维细胞生长因子的插入融合通过抑制剂相互作用的空间阻断赋予核糖核酸酶1增强的细胞毒性。

• 发表时间: 2004
• 期刊: FEBS Lett 568(1-3)
• 作者: T.Matsumoto;et al.;Junichiro Futami;Junichiro Futami;Tadanori Yamada;Lei Li;Shin-ichi Miyoshi;Hiroko Tada
• 通讯作者: Hiroko Tada

Reversal of streptozotocin-induced hyperglycemia by transplantation of pseudoislets consisting of beta cells derived from ductal cells.

通过移植由导管细胞衍生的β细胞组成的假胰岛来逆转链脲佐菌素诱导的高血糖。

• 发表时间: 2004
• 期刊: Endocr J. 51(3)
• 作者: T.Matsumoto;et al.;Junichiro Futami;Junichiro Futami;Tadanori Yamada;Lei Li;Shin-ichi Miyoshi;Hiroko Tada;Takeshi Ogata
• 通讯作者: Takeshi Ogata

S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes.

S100C/A11 是 Ca(2+) 诱导的人表皮角质形成细胞生长抑制的关键介质。

• DOI: 10.1083/jcb.200304017
• 发表时间: 2003-11-24
• 期刊: JOURNAL OF CELL BIOLOGY
• 影响因子: 7.8
• 作者: Sakaguchi, M;Miyazaki, M;Takaishi, M;Sakaguchi, Y;Makino, E;Kataoka, N;Yamada, H;Namba, M;Huh, NH
• 通讯作者: Huh, NH