Micelle surface engineering for active targeting by acidic tumor extracellular pH
胶束表面工程通过酸性肿瘤细胞外 pH 值主动靶向
基本信息
- 批准号:7130778
- 负责人:
- 金额:$ 26.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-08-22 至 2011-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): This application proposes to create and assess a new mode of active targeting for anticancer agents to solid tumors that develop an acidic extracellular environment. The current paradigm of active tumor targeting technology in chemotherapy is based on active internalization of drug carriers into cells by binding between a tumor specific antigen and its monoclonal antibody (mAb) or between a ligand and its corresponding receptor. In an attempt to shift this paradigm, an intelligent polymeric micelle system will be devised. The micelle will hide a particular moiety during circulation, which has the strong capability to translocate the micelle into cells, and expose the moiety in the tumor extracellular environment to facilitate the internalization process. Thus, micelle technology turns a non-specific cell internalizing vector into a tumor specific tool. For this purpose, the slightly acidic tumor extracellular pH (pHe: pH 6.6-7.0) has been selected as a triggering signal for exposure of the moiety because this acidity is natural in most solid tumors and is confined to extracellular space. This new system will broaden the range of solid tumors that can be treated using targeted chemotherapy and it is expected to replace cumbersome and expensive mAb-based targeting technology. The goal of this application is to design and construct a super pH-sensitive surface on a micelle core structure to provide exposure mechanisms for an internalizing agent. When this technology is successful, the micelle system will be capable of targeting anticancer drugs to most solid tumors that have pHe values below 7.0. This triggering pH was found to be reasonable, judging from our feasibility results obtained from two different micelle systems. In this application, a model cell penetrating peptide (CPP) TAT is utilized, which does not require particular antigens or receptors for cellular localization.
描述(由申请人提供):本申请提出创建并评估抗癌剂主动靶向形成酸性细胞外环境的实体瘤的新模式。化疗中的主动肿瘤靶向技术的当前范例是基于通过肿瘤特异性抗原与其单克隆抗体(mAb)之间或配体与其相应受体之间的结合将药物载体主动内化到细胞中。在试图改变这种模式,智能聚合物胶束系统将被设计。胶束在循环过程中会隐藏一个特定的部分,它具有很强的能力将胶束转运到细胞内,并将该部分暴露在肿瘤细胞外环境中以促进内化过程。因此,胶束技术将非特异性细胞内化载体转变为肿瘤特异性工具。为此,选择微酸性肿瘤细胞外pH值(pHe:pH 6.6-7.0)作为暴露该部分的触发信号,因为这种酸性在大多数实体瘤中是天然的,并局限于细胞外空间。这种新系统将扩大可以使用靶向化疗治疗的实体肿瘤的范围,并有望取代繁琐而昂贵的基于mAb的靶向技术。本申请的目标是在胶束核心结构上设计和构建超pH敏感表面,以提供内化剂的暴露机制。当这项技术成功时,胶束系统将能够将抗癌药物靶向大多数pHe值低于7.0的实体肿瘤。这个触发pH值被认为是合理的,从我们的可行性结果从两个不同的胶束系统得到的判断。在本申请中,使用模型细胞穿透肽(CPP)达特,其不需要特定的抗原或受体用于细胞定位。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)
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You Han Bae其他文献
“On–Off“ Thermocontrol of Solute Transport. II. Solute Release from Thermosensitive Hydrogels
- DOI:
10.1023/a:1015860824953 - 发表时间:
1991-01-01 - 期刊:
- 影响因子:4.300
- 作者:
You Han Bae;Teruo Okano;Sung Wan Kirn - 通讯作者:
Sung Wan Kirn
Cancer targeting paradigm: does it need to be shifted?
- DOI:
10.1016/j.nano.2007.10.041 - 发表时间:
2007-12-01 - 期刊:
- 影响因子:
- 作者:
You Han Bae - 通讯作者:
You Han Bae
Low‐temperature processable biodegradable block copolymers embedded with proteins
嵌入蛋白质的可低温加工的可生物降解的嵌段共聚物
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:0
- 作者:
Yu Matsumoto;Joseph W. Nichols;Kazuko Toh;Takahiro Nomoto;Horacio Cabral;Yutaka Miura;R. James Christie;Naoki Yamada;Tadayoshi Ogura;Mitsunobu R. Kano;Yasuhiro Matsumura;Nobuhiro Nishiyama;Tatsuya Yamasoba;You Han Bae;Kazunori Kataoka;Yasuhiko Iwasaki - 通讯作者:
Yasuhiko Iwasaki
“On–Off” Thermocontrol of Solute Transport. I. Temperature Dependence of Swelling of N-Isopropylacrylamide Networks Modified with Hydrophobic Components in Water
- DOI:
10.1023/a:1015871732706 - 发表时间:
1991-01-01 - 期刊:
- 影响因子:4.300
- 作者:
You Han Bae;Teruo Okano;Sung Wan Kim - 通讯作者:
Sung Wan Kim
Hydrogels: Swelling, Drug Loading, and Release
- DOI:
10.1023/a:1015887213431 - 发表时间:
1992-01-01 - 期刊:
- 影响因子:4.300
- 作者:
Sung Wan Kim;You Han Bae;Teruo Okano - 通讯作者:
Teruo Okano
You Han Bae的其他文献
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{{ truncateString('You Han Bae', 18)}}的其他基金
WELL-DEFINED MULTIFUNCTIONAL POLYMERIC NANOCARRIERS FOR EFFECTIVE GENE DELIVERY
明确的多功能聚合物纳米载体可实现有效的基因传递
- 批准号:
8257580 - 财政年份:2009
- 资助金额:
$ 26.54万 - 项目类别:
WELL-DEFINED MULTIFUNCTIONAL POLYMERIC NANOCARRIERS FOR EFFECTIVE GENE DELIVERY
明确的多功能聚合物纳米载体可实现有效的基因传递
- 批准号:
7817124 - 财政年份:2009
- 资助金额:
$ 26.54万 - 项目类别:
Intelligent Polymeric Nanogel Technology Overcoming Drug Resistance in Ovarian Ca
智能聚合物纳米凝胶技术克服卵巢钙耐药性
- 批准号:
7696849 - 财政年份:2009
- 资助金额:
$ 26.54万 - 项目类别:
WELL-DEFINED MULTIFUNCTIONAL POLYMERIC NANOCARRIERS FOR EFFECTIVE GENE DELIVERY
明确的多功能聚合物纳米载体可实现有效的基因传递
- 批准号:
8085835 - 财政年份:2009
- 资助金额:
$ 26.54万 - 项目类别:
A novel approach for long term protein delivery
一种长期蛋白质输送的新方法
- 批准号:
7141503 - 财政年份:2006
- 资助金额:
$ 26.54万 - 项目类别:
A novel approach for long term protein delivery
一种长期蛋白质输送的新方法
- 批准号:
7664879 - 财政年份:2006
- 资助金额:
$ 26.54万 - 项目类别:
Micelle surface engineering for active targeting by acidic tumor extracellular pH
胶束表面工程通过酸性肿瘤细胞外 pH 值主动靶向
- 批准号:
7279446 - 财政年份:2006
- 资助金额:
$ 26.54万 - 项目类别:
A novel approach for long term protein delivery
一种长期蛋白质输送的新方法
- 批准号:
7269465 - 财政年份:2006
- 资助金额:
$ 26.54万 - 项目类别:
Micelle surface engineering for active targeting by acidic tumor extracellular pH
胶束表面工程通过酸性肿瘤细胞外 pH 值主动靶向
- 批准号:
7893033 - 财政年份:2006
- 资助金额:
$ 26.54万 - 项目类别:
A novel approach for long term protein delivery
一种长期蛋白质输送的新方法
- 批准号:
7472401 - 财政年份:2006
- 资助金额:
$ 26.54万 - 项目类别:
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