为基于蛋白质的疗法优化酶反应聚合体。

Nanomedicine (London, England) Pub Date : 2024-02-01 Epub Date: 2024-01-25 DOI:10.2217/nnm-2023-0300
Dorian Foster, Alaura Cakley, Jessica Larsen
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引用次数: 0

摘要

目的:刺激响应型聚合体是一种很有前景的基于蛋白质的治疗工具,但需要对其病理响应行为进行更深入的了解和优化。材料与方法:比较了由不同分子量的透明质酸(HA)嵌段共聚物自组装而成的透明质酸(HA)-聚(b-乳酸)(PLA)聚合体的物理性质、降解和细胞内行为。结果显示主要结果显示,随着分子量的降低,酶反应性也随之增加。主要的配方差异如下:HA(5 kDa)-PLA 配方显示出最明显的包裹蛋白质释放,而 HA(7 kDa)-PLA 配方显示出与中性最不同的释放行为。结论:我们发现了HA-PLA聚合体输送蛋白质的设计规则,分子量越低,封装效率越高,释放量越大,细胞内吸收量也越大。
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Optimizing enzyme-responsive polymersomes for protein-based therapies.

Aims: Stimuli-responsive polymersomes are promising tools for protein-based therapies, but require deeper understanding and optimization of their pathology-responsive behavior. Materials & methods: Hyaluronic acid (HA)-poly(b-lactic acid) (PLA) polymersomes self-assembled from block copolymers of varying molecular weights of HA were compared for their physical properties, degradation and intracellular behavior. Results: Major results showed increasing enzyme-responsivity associated with decreasing molecular weight. The major formulation differences were as follows: the HA(5 kDa)-PLA formulation exhibited the most pronounced release of encapsulated proteins, while the HA(7 kDa)-PLA formulation showed the most different release behavior from neutral. Conclusion: We have discovered design rules for HA-PLA polymersomes for protein delivery, with lower molecular weight leading to higher encapsulation efficiency, greater release and greater intracellular uptake.

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