SBIR Phase I: A Novel Method for Identifying Synthetic Binding Agents for Targeting Drugs to Specific Tissues

SBIR 第一阶段：一种识别合成结合剂的新方法，用于将药物靶向特定组织

• 批准号: 1416082
• 负责人: Hong Zhong
• 金额: $ 15万
• 依托单位: Parabon NanoLabs, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1416082&HistoricalAwards=false
• 关键词: SBIR; Phase; Novel; Method; Identifying

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is the development of a screening method to reliably identify binding agents that can be used to target drugs to specific tissues or cell types. Targeting drugs can increase their effectiveness and reduce their side effects, thus it is important to develop methods that can screen for binding agents that can be used to enhance drugs that would otherwise have systemic activity. Existing methods do not attempt to replicate the environment in which binding agents are used, therefore agents that appear promising in the lab often fail in the clinic. The screening method incorporates a nano-scale drug carrier (i.e., nanocarrier) into the screening process, so that binding agents attached to it that perform well during screening can be expected to perform well in practice. A reliable drug targeting system of the type proposed could have enormous commercial value. Some analysts believe nanocarriers will account for 40% of a $136 billion nanotechnology-enabled drug delivery market by 2021. Because the benefits of targeted drug delivery over equivalent non-targeted systems are expected to be substantial, targeted nanocarriers are expected to account for most of this vast market.This SBIR project aims to produce a targeted drug delivery system that is a first-of-its-kind in situ target ligand screening procedure. Targeted drug delivery is one of the most promising strategies for optimizing drug efficacy with minimal side effects, but current screening techniques for identifying highly specific targeting ligands suffer two drawbacks: (1) they only detect individual, high-affinity binding ligands (whereas well-organized, controllable, multiple, low-affinity/high-affinity binding ligands used in plurality are thought to provide the optimal specificity and inhibition); and (2) the manner in which they present ligands during screening in no way approximates the way ligands are presented in a targeted drug formulation, which leads to a high failure rate. The method developed in this project remedies these issues by (a) producing a screening library that employs precisely controlled nanocarriers, each type decorated with a unique collection of identical targeting ligands, and (b) employing as a targeted delivery vehicle or inhibitor, the nanocarrier with the optimal preferential binding affinity for a given target as identified during screening. This is the first method for developing a targeted nanocarrier that employs this type of in situ ligand screening.

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力是开发一种筛选方法，以可靠地识别可用于将药物靶向特定组织或细胞类型的结合剂。 靶向药物可以增加其有效性并减少其副作用，因此重要的是开发可以筛选可用于增强原本具有全身活性的药物的结合剂的方法。 现有的方法不试图复制使用结合剂的环境，因此在实验室中看起来有希望的试剂在临床上经常失败。 该筛选方法结合了纳米级药物载体（即，纳米载体）引入到筛选过程中，使得在筛选过程中表现良好的与其连接的结合剂可以预期在实践中表现良好。 这种可靠的药物靶向系统可能具有巨大的商业价值。一些分析师认为，到2021年，纳米载体将占1360亿美元纳米技术药物输送市场的40%。 由于靶向给药系统相对于非靶向给药系统的优势是巨大的，因此靶向纳米载体有望占据这一巨大市场的大部分。SBIR项目旨在生产一种靶向给药系统，这是第一种原位靶向配体筛选程序。 靶向药物递送是在副作用最小的情况下优化药物功效的最有前途的策略之一，但目前用于鉴定高度特异性靶向配体的筛选技术存在两个缺点：（1）它们仅检测单个的高亲和力结合配体（而被认为以多种方式使用的良好组织的、可控的、多种的、低亲和力/高亲和力结合配体提供最佳的特异性和抑制）;和（2）它们在筛选过程中呈递配体的方式与靶向药物制剂中呈递配体的方式完全不同，这导致高失败率。该项目中开发的方法通过以下方式解决了这些问题：（a）产生采用精确控制的纳米载体的筛选文库，每种类型用相同靶向配体的独特集合修饰，和（B）采用作为靶向递送载体或抑制剂的纳米载体，所述纳米载体对筛选期间鉴定的给定靶具有最佳优先结合亲和力。 这是第一种采用这种类型的原位配体筛选来开发靶向纳米载体的方法。