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)
基本信息
- 批准号:20015045
- 负责人:
- 金额:$ 6.08万
- 依托单位:
- 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:
- 关键词:
项目摘要
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.
我们制备了两种具有抗HO-1和抗肿瘤活性的聚合物药物:(I)聚乙二醇化的(共价键合的)锌PP胶束和(Ii)SMA-锌PP胶束。细胞在SMA-ZnPP胶束中的摄取速度是聚乙二醇锌PP结合物的几倍。它们具有体外细胞毒性和体内抗肿瘤活性,体内IC_(50)分别为1~7μM和10 mg/kg。在420 nm的LED照射下,它们对培养的人肿瘤细胞(CML细胞系K562、ATL细胞系MT-2、食管腺癌细胞系Kyse 510)也显示出较强的细胞毒性。在体内和体外实验中,SMA-ZPP加LED在420 nm处对小鼠肿瘤的抑制作用均比单纯药物更有效。共价的聚乙二醇锌多糖偶联物在肿瘤组织中被丝氨酸和硫醇蛋白水解酶分解,释放出游离的锌多酚,而SMA-锌多聚多糖胶束与卵磷脂等细胞膜成分接触后胶束解体,在细胞内有效地释放药物锌多酚。
项目成果
期刊论文数量(89)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
成人T細胞白血病細胞に対するミセル化亜鉛プロトポルフィリンの増殖抑制作用
胶束锌原卟啉对成人T细胞白血病细胞的抗增殖作用
- DOI:
- 发表时间:2009
- 期刊:
- 影响因子:0
- 作者:覃海波;方軍;中村秀明;前田浩
- 通讯作者:前田浩
成人T細胞白血病細胞に対するミセル化亜鉛プロトポルフィリンの増殖抑制作用(Growth inhibition of pegylated zinc protoporphyrin(PEG-ZnPP)on adult T-cell leukemia cells)
聚乙二醇化锌原卟啉 (PEG-ZnPP) 对成人 T 细胞白血病细胞的生长抑制
- DOI:
- 发表时间:2009
- 期刊:
- 影响因子:0
- 作者:覃海波;方軍;中村秀明;前田浩
- 通讯作者:前田浩
ニトログリセリン軟膏塗布による癌局所でのEPR効果増強に基づく制癌剤のデリバリーと治療効果の増強
通过应用硝酸甘油软膏增强癌症局部EPR效果来输送抗癌药物并提高疗效
- DOI:
- 发表时间:2009
- 期刊:
- 影响因子:0
- 作者:前田浩;等
- 通讯作者:等
Oxystress-induced antitumor therapeutics via targeted-inhibiting heme oxygenase-1(HSP32)in tumor
通过靶向抑制肿瘤血红素加氧酶-1 (HSP32) 进行氧应激诱导的抗肿瘤治疗
- DOI:
- 发表时间:2008
- 期刊:
- 影响因子:0
- 作者:P. Valent;他;矢守隆夫.;方軍他
- 通讯作者:方軍他
Oxystress-induced antitumor therapeutics via targeted-inhibiting heme oxygenase-1 (HSP32) in tumor
通过靶向抑制肿瘤中的血红素加氧酶-1 (HSP32) 进行氧应激诱导的抗肿瘤治疗
- DOI:
- 发表时间:2008
- 期刊:
- 影响因子:0
- 作者:方軍;他
- 通讯作者:他
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MAEDA Hiroshi其他文献
MAEDA Hiroshi的其他文献
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{{ truncateString('MAEDA Hiroshi', 18)}}的其他基金
Growth inhibition of selected bacterial species by peptide nucleic acids for control of oral microflora
通过肽核酸抑制选定细菌种类的生长以控制口腔微生物区系
- 批准号:
15K11404 - 财政年份:2015
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Application of antisense PNA as antibiotics against periodontal pathogens
反义PNA作为牙周病原菌抗生素的应用
- 批准号:
24659925 - 财政年份:2012
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Influence to a wrist joint by the topspin technology in tennis
网球上旋技术对腕关节的影响
- 批准号:
23500739 - 财政年份:2011
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Cross reactivity of archaeal chaperonin with human CCT involved in the pathogenesis of periodontitis and autoimmune disease
古菌伴侣蛋白与人类 CCT 的交叉反应参与牙周炎和自身免疫性疾病的发病机制
- 批准号:
21592624 - 财政年份:2009
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
New miceller agent for antioxidation therapy based on XO inhibition using AHPP
基于 AHPP 的 XO 抑制的新型抗氧化治疗胶束剂
- 批准号:
20590049 - 财政年份:2008
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular cloning and functional analysis of non-coding RNA expressed in periodontal bacteria
牙周细菌表达非编码RNA的分子克隆及功能分析
- 批准号:
19592387 - 财政年份:2007
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The effect on human body at the impact of tennis racket and balls from the viewpoints of mechanical characteristics of the grip
从握把力学特性看网球拍与球撞击时对人体的影响
- 批准号:
16500415 - 财政年份:2004
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A High-Precision and High-Speed Stereo Matching Algorithm Based on Synergetics and its Application to Automatic Production of Rough 3 D City Area Map
基于协同学的高精度高速立体匹配算法及其在城市三维粗图自动制作中的应用
- 批准号:
16500133 - 财政年份:2004
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Control of Nanoscale Structures of Amphiphilic Self-Assembly by Physical Factors
物理因素对两亲性自组装纳米结构的控制
- 批准号:
12440200 - 财政年份:2000
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Research on the role of NO in microbial pathogenesis
NO在微生物发病机制中的作用研究
- 批准号:
12470065 - 财政年份:2000
- 资助金额:
$ 6.08万 - 项目类别:
Grant-in-Aid for Scientific Research (B)