Development of a facile strategy to synthesize PLA-based reduction-responsive shell-sheddable nanoassemblies for drug delivery****

开发一种简单的策略来合成用于药物输送的基于 PLA 的还原响应可脱壳纳米组件****

• 批准号: 537993-2018
• 负责人: Oh, JungKwon
• 金额: $ 1.82万
• 依托单位: Concordia University
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=661148
• 关键词: Development; facile; strategy; synthesize; PLA

Current trend in polymer-based nanomedicine for cancer therapy mainly focuses on the development of block copolymer-based nanoassemblies with hydrophobic cores enabling the encapsulation of hydrophobic anticancer drugs. Recently, well-defined block copolymers consisting of hydrophobic polylactide (PLA) and hydrophilic poly(ethylene glycol) (PEG) blocks have been currently practiced in clinics. However, the conventional systems rely on diffusion-controlled mechanism, which is passive, uncontrolled, and slow for the release of encapsulated anticancer drugs. The research opportunity here is to explore reduction-responsive degradation platform for cancer therapy with enhanced/controlled drug release profile. ****In this proposed research, in collaboration with Advanced Polymeric Materials (APM) located in Montreal, we will explore a facile strategy to incorporate disulfide linkage into the design of conventionally-designed PLA-b-PEG block copolymers. The strategy will utilize a combination of click-type alkyne-azido cycloaddition reaction with ring opening polymerization to synthesize novel block copolymer having a reduction-responsive disulfide linkage (SS) at the junction of PLA and PEG blocks, thus PLA-SS-PEG block copolymers. Important parameters including block lengths and the number of alkyl groups adjacent to SS linkage will be varied to understand the structure-property relationship. Further, the synthesized copolymers will be evaluated for effective intracellular drug delivery. This collaborative project will offer APM a great opportunity to be competitive in markets over their competitors.

目前，基于聚合物的纳米药物用于癌症治疗的趋势主要集中在开发具有疏水核的基于嵌段共聚物的纳米组装体，使得能够包封疏水抗癌药物。最近，由疏水性聚乳酸（PLA）和亲水性聚（乙二醇）（PEG）嵌段组成的定义明确的嵌段共聚物目前已被应用于临床。然而，传统的系统依赖于扩散控制机制，其对于包封的抗癌药物的释放是被动的、不受控制的和缓慢的。本研究的目的是探索具有增强/控制药物释放特性的还原响应性降解平台用于癌症治疗。* 在这项拟议的研究中，我们将与位于蒙特利尔的高级聚合材料（APM）合作，探索一种简单的策略，将二硫键纳入传统设计的PLA-b-PEG嵌段共聚物的设计中。该策略将利用点击型炔-叠氮基环加成反应与开环聚合的组合来合成在PLA和PEG嵌段的连接处具有还原响应性二硫键（SS）的新型嵌段共聚物，因此PLA-SS-PEG嵌段共聚物。重要的参数，包括嵌段长度和相邻的SS键的烷基基团的数目将被改变，以了解结构-性质的关系。此外，将评价合成的共聚物的有效细胞内药物递送。这个合作项目将为APM提供一个很好的机会，使其在市场上比竞争对手更具竞争力。