Development of zinc protoporphyrin micelles for cancer photodymanic therapy with xenon light

开发用于氙光癌症光动力治疗的锌原卟啉胶束

• 批准号: 22700927
• 负责人: FANG Jun
• 金额: $ 2.5万
• 依托单位: Sojo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22700927/
• 关键词: ドラッグデリバリー; 光化学療法

In this study, by comparing the physiochemical characteristics, stability as well as in vivo pharmacokinetics of different ZnPP micelles, we found that HPMA-ZnPP, with the particle size of about 80 nm, showed good stability in circulation, resulting in prolonged plasma half-life as well as tumor-selective accumulation (EPR effect). We thus selected HPMA-ZnPP for further development. In vitro studies using Hela cells exhibited a strong cytotoxicity of HPMA-ZnPP upon light irradiation. In vivo experiments showed an HPMA-ZnPP dose-dependent and irradiation dependent (intensity and duration) suppression of tumor growth. Moreover, the tumor-selective accumulation of HPMA-ZnPP was clearly detected in an in vivo imaging system. Token together, these findings strongly suggest the potential of HPMA-ZnPP as a new PDT drug for cancer, at the same time with tumor-detecting potency.

本研究通过比较不同ZnPP胶束的理化特性、稳定性以及体内药代动力学，发现粒径约为80 nm的HPMA-ZnPP在循环中表现出良好的稳定性，导致血浆半衰期延长以及肿瘤选择性蓄积（EPR效应）。因此，我们选择HPMA-ZnPP进行进一步开发。使用Hela细胞的体外研究在光照射时表现出HPMA-ZnPP的强细胞毒性。体内实验显示HPMA-ZnPP对肿瘤生长的剂量依赖性和辐射依赖性（强度和持续时间）抑制。此外，在体内成像系统中清楚地检测到HPMA-ZnPP的肿瘤选择性积累。总之，这些发现强烈表明HPMA-ZnPP作为一种新的PDT癌症药物的潜力，同时具有肿瘤检测效力。

项目成果

The EPR effect as seen by tumor imaging of fluorescent proteins and synthetic nanoparticles.

通过荧光蛋白和合成纳米颗粒的肿瘤成像观察到的 EPR 效应。

• 发表时间: 2012
• 作者: Maeda H;Nakamura H;Qin H;Tsukigawa K;Fang J.
• 通讯作者: Fang J.

水溶性亜鉛プロトポルフィリンミセルによる抗腫瘍効果とLED光源420nmによる光増感作用

水溶性锌原卟啉胶束的抗肿瘤作用及420nm LED光源的光敏作用

• 发表时间: 2010
• 作者: Tsukigawa K;Nakamura H;Fang J;Shinkai S;Maeda H.;覃海波
• 通讯作者: 覃海波

Pegylated Zinc Protoporphyrin: A Micelle-Forming Polymeric Drug for Cancer Therapy

聚乙二醇化锌原卟啉：一种用于癌症治疗的胶束形成聚合物药物

• DOI: 10.1201/b13159-5
• 发表时间: 2012
• 期刊: Proceedings of the National Academy of Sciences
• 作者: Jun Fang;Hideaki Nakamura;T. Seki;Haibo Qin;G. Bharate;H. Maeda
• 通讯作者: H. Maeda

The EPR effect and beyond for cancer selective drug delivery and imaging

EPR 效应及癌症选择性药物输送和成像的其他作用

• 发表时间: 2013
• 作者: Hideaki Nakamura;Jun Fang;et al;Hiroshi Maeda
• 通讯作者: Hiroshi Maeda

Tumor targeting polymeric drugs based on the EPR effect; its augmentation for drug delivery and efficacy, and extension to tumor imaging

基于EPR效应的肿瘤靶向高分子药物；

• 发表时间: 2012
• 作者: Maeda H;Nakamura H;Qin H;Tsukigawa K;Fang J.;Hiroshi Maeda
• 通讯作者: Hiroshi Maeda