Molecular Recognition in Dendrimers Based on Melamine

基于三聚氰胺的树枝状聚合物的分子识别

• 批准号: 6547605
• 负责人: ERIC E SIMANEK
• 金额: $ 25.46万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6547605
• 关键词: antineoplastics; chemical conjugate; chemical structure function; chemical synthesis; combinatorial chemistry; drug screening /evaluation; drug vehicle; pharmacokinetics; polymers; resin; solubility; triazines

DESCRIPTION (provided by applicant): The efforts proposed describe the thorough investigation of a class of dendrimers to determine whether these monodisperse, engineerable macromolecules are suitable vehicles for drug delivery. Their size suggests that the EPR effect can be exploited to target tumors. The ability to decorate these architectures with homing peptides allows for the investigation of "magic bullet" stategies. The proposal focuses on Pt-coordination complexes, as the collaborator has great interest in this agent. The biological studies will be executed by the collaborator in conjunction with students from the PI's laboratory.This proposal addresses two specific aims: 1) Can the dendrimers be targeted to tumors using passive and/or active strategies? The enhanced permeability and retention of polymers by tumors offers a passive mechanism for targeting these tissues for destruction. Attaching homing peptides to the polymeric drug delivery vehicle offers an additional active strategy to further discriminate the diseased tissue from host tissue. These experiments will be executed by looking at the biodistribution of labeled dendrimers that differ in size and composition. Strategies for screening compositions efficiently, and evaluating libraries of homing peptides are described. 2) Can the dendrimers be loaded with cytotoxins and display suitable anticancer activity? Platinum will be loaded using dendrimers through pendant malonate groups. Release from the malonate is triggered in response to a change in pH. Other cytotoxins will be conjugated using reversible or biolabile linkages. The ability of these dendrimers to noncovalently sequester anticancer agents is also explored.

描述（由申请人提供）：拟议的努力描述了对一类树枝状聚合物的彻底调查，以确定这些单分散的，可工程的大分子是否是适合输送药物的车辆。它们的大小表明可以将EPR效应利用为靶肿瘤。用归巢肽装饰这些架构的能力可以调查“魔术子弹”状态。该提案的重点是PT协调络合物，因为合作者对该代理人非常感兴趣。合作者将与PI实验室的学生一起执行生物学研究。该提案针对两个具体的目的：1）树枝状聚合物是否可以使用被动和/或活跃策略将树枝状聚合物针对肿瘤？肿瘤对聚合物的渗透性增强和保留提供了一种被动的机制，可将这些组织靶向破坏。将归巢肽连接到聚合物药物输送车上，提供了另一种主动策略，以进一步区分患病组织与宿主组织。这些实验将通过查看大小和组成不同的标记树状聚合物的生物分布来执行。描述了有效筛选组成的策略，并评估归巢肽的文库。 2）树枝状聚合物是否可以装有细胞毒素并显示合适的抗癌活性？ 铂将通过垂体丙酸酯组使用树突聚合物加载。响应于pH的变化而触发从丙二酯释放。其他细胞毒素将使用可逆或生物抗体链接结合。还探讨了这些树枝状聚合物非共价隔离抗癌剂的能力。