Macromolecular anticancer agent, PEGylated Zinc protoporphyrin (ZnP) targeting HSP32

靶向HSP32的高分子抗​​癌剂聚乙二醇化锌原卟啉（ZnP）

• 批准号: 20015045
• 负责人: MAEDA Hiroshi
• 金额: $ 6.08万
• 依托单位: Sojo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20015045/
• 关键词: HSP32阻害剤; HO-1阻害剤; 高分子型制癌剤; DDS; 腫瘍ターゲッティング; Znプロトポルフィリン; 新しい光化学療法; PEG化制癌剤; 腫瘍ターゲラィング; 腫瘍ターゲティング

We prepared two types of polymeric drugs having anti-HO-1 and antitumor activities, (i) PEGylated ZnPP (covalently linked ) and (ii) SMA-ZnPP micelles. Cell uptake was several fold faster in SMA-ZnPP micelles than PEG-ZnPP conjugates. They exhibited both in vitro cytotoxicity and in vivo antitumor activity having IC_<50> of 1-7μM and 10mg/kg in vivo respectively. They also exhibited enhanced cytotoxicity to human tumor cells (CML cell line, K562 ; ATL cell line, MT-2 ; esophageal cell line, Kyse 510) in culture under the exposure to LED light at 420nm. Mouse tumors were more effectively suppressed with SMA-ZnPP plus LED light at 420nm than drug alone both in vivo and in vitro. PEG-ZnPP conjugates (covalent) undergo hydrolytic cleavage by serine and thiol proteases in the tumor tissue and released free ZnPP, whereas SMA-ZnPP micelles underwent micelle disintegration upon the contact with to cell membrane components such as lecithin, and released the drug ZnPP effectively in cells.

我们准备了具有抗HO-1和抗肿瘤活性的两种类型的聚合物药物：（i）Pegypated Znpp（共价连接）和（ii）SMA-ZNPP胶束。在SMA-ZNPP胶束中，细胞摄取比PEG-ZNPP结合物快几倍。他们分别在体外暴露了体外细胞毒性和体内抗肿瘤活性，分别为1-7μm和10mg/kg体内。他们还向人类肿瘤细胞（CML细胞系，K562； ATL细胞系，MT-2；食管510，KYSE 510）暴露了增强的细胞毒性，在420nm的LED光线下培养。与单独的体内和体外药物相比，SMA-ZNPP和LED光在420nm处更有效地抑制了小鼠肿瘤。 PEG-ZNPP结合物（共价）在肿瘤组织中通过丝氨酸和硫醇蛋白酶进行水解裂解，并释放自由ZNPP，而SMA-Znpp胶束在与细胞膜成分接触时经历了胶束分解，例如细胞膜成分，例如Lecithin，并释放出卵裂蛋白，并释放出药物ZNPPP的细胞，并有效地在Prunpppp中。

项目成果

高分子薬剤のEPR効果による腫瘍デリバリーと癌治療

利用聚合物药物的 EPR 效应进行肿瘤递送和癌症治疗

• 发表时间: 2008
• 期刊: 血管医学 Vol.911月号
• 作者: 前田浩;関孝弘
• 通讯作者: 関孝弘

Immunostimulation-mediated antitumor activity by preconditioning with rice-shochu distillation residue against implanted tumor in mice.

用大米烧酒蒸馏残渣预处理对小鼠植入肿瘤的免疫刺激介导的抗肿瘤活性。

• 发表时间: 2008
• 期刊: utrit. Cancer 60
• 作者: T. Seki;et al;H. Maeda(6/7番目);K. Kida
• 通讯作者: K. Kida

Current problems in cancer chemotherapy and new developments toward more cancer selective drug targeting based on EPR-effect

癌症化疗的当前问题以及基于 EPR 效应的更多癌症选择性药物靶向的新进展

• 发表时间: 2009
• 作者: 大場岳彦;中村裕;右田敏郎;奥村栄;矢守隆夫;石川雄一;清宮啓之;H. Maeda
• 通讯作者: H. Maeda

Tumor selective targeting using macromolecular drugs based on EPR effect: Future solutions for solid tumor chemotherapy

基于EPR效应的大分子药物肿瘤选择性靶向：实体瘤化疗的未来解决方案

• 发表时间: 2009
• 作者: Seimiya;H.;Ohishi;T.;Tsuruo;T.;H. Maeda
• 通讯作者: H. Maeda

Tumor selective targeting using macromolecular drugs based on EPR effect : Future solutions for solid tumor chemotherapy

基于EPR效应的大分子药物肿瘤选择性靶向：实体瘤化疗的未来解决方案

• 发表时间: 2009
• 作者: 川谷誠;青野晴美;矢守隆夫;長田裕之;清宮啓之;前田浩
• 通讯作者: 前田浩