Development of a novel type worm-like DDS penetrable into tumor tissue

一种可穿透肿瘤组织的新型蠕虫状DDS的开发

• 批准号: 23390014
• 负责人: KOGURE Kentaro
• 金额: $ 11.98万
• 依托单位: Kyoto Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390014/
• 关键词: ナノDDS; 癌細胞間隙; 癌微小環境; 癌治療; siRNA

In this study, we attempted to develop a novel type worm-like DDS for overcoming drawbacks of conventional nanoDDS for anticancer therapy, such as, antigenicity of PEG, low cell affinity and low permeability into tumor tissue. As the results, we successfully developed charge-invertible liposomes, which can response to tumor microenvironment, and the capabilities of endosomal escape and cellular internalization and tumor accumulation comparable to PEG-liposomes were confirmed. Moreover, the worm-like nanostructures, which can penetrate into narrow space, were developed, and significantly high permeability into spheroids was achieved by improvement of physicochemical property of wick structure, modification with hyaluronidase and functional peptides. Then, integration of those functional liposomes, and evaluation of in vivo functionality was started.

本研究针对传统纳米给药系统存在的PEG抗原性差、细胞亲和性差、对肿瘤组织渗透性差等缺点，开发了一种新型蠕虫状给药系统。因此，我们成功地开发了电荷可逆脂质体，它可以响应于肿瘤微环境，并证实了与PEG-脂质体相当的内体逃逸和细胞内化以及肿瘤蓄积的能力。此外，通过改善灯芯结构的理化性质、透明质酸酶和功能肽的修饰，开发出了可渗透到狭窄空间的蠕虫状纳米结构，并实现了对球体的显著高渗透性。然后，开始这些功能性脂质体的整合和体内功能性的评价。

项目成果

A flexible nano carrier for siRNA delivery into tumor

用于将 siRNA 递送至肿瘤的柔性纳米载体

• 发表时间: 2013
• 作者: Hayato Koganei;Shoji Tachikawa;Minoru Suzuki;Koji Ono;Hiroyuki Nakamura;吉永 将・頼経健一・竹川 薫;Kogure K. Shimatani Y. Uno K. Chon H.K. Hama S
• 通讯作者: Kogure K. Shimatani Y. Uno K. Chon H.K. Hama S

腫瘍内部への浸透を目指した新規siRNAキャリアーの開発

开发一种新的siRNA载体，旨在渗透到肿瘤中

• 发表时间: 2013
• 作者: ○村井健一;松下知世;中村 光;兵後訓道;中島淳起;藤岡弘道;宇野晃平
• 通讯作者: 宇野晃平

組織狭小空間への送達を目指したsiRNAキャリアーの開発

开发旨在递送至狭窄组织空间的 siRNA 载体

• 发表时间: 2012
• 作者: Nishikawa M;Takahashi Y;Takakura Y;小暮健太朗
• 通讯作者: 小暮健太朗

A touch-and-go lipid wrapping technique in microfluidic channels for rapid fabrication of multifunctional envelope-type gene delivery nanodevices

• DOI: 10.1039/c1lc20392d
• 发表时间: 2011-01-01
• 期刊: LAB ON A CHIP
• 影响因子: 6.1
• 作者: Kitazoe, Katsuma;Wang, Jun;Baba, Yoshinobu
• 通讯作者: Baba, Yoshinobu

Efficient Intradermal Delivery of Superoxide Dismutase Using a Combination of Liposomes and Iontophoresis for Protection against UV-Induced Skin Damage

• DOI: 10.1248/bpb.35.781
• 发表时间: 2012-05-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Kigasawa, Kaoru;Miyashita, Moeko;Kogure, Kentaro
• 通讯作者: Kogure, Kentaro