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Steric stabilization of bioactive nanoparticles using elastin-like polypeptides
Advanced Drug Delivery Reviews ( IF 16.1 ) Pub Date : 2024-01-26 , DOI: 10.1016/j.addr.2024.115189
Alvin Phan , J. Andrew MacKay

Elastin-like polypeptides (ELP) are versatile, thermo-responsive polymers that can be conjugated to virtually any therapeutic cargo. Derived from short amino-acid sequences and abundant in humans, certain ELPs display low immunogenicity. Substrates for endogenous proteases, ELPs are biodegradable and thus, are candidate biomaterials. Peptides and proteins can be directly coupled with ELPs through genetic engineering, while other polymers and small molecules can be appended through covalent bioconjugation or non-covalent complexation. ELPs that phase separate at physiological temperatures can form the core of nano assemblies; however, ELPs that remain soluble can sterically stabilize the corona of a variety of nanoparticles. Nanoparticles with ELPs at their corona promote colloids with favorable pharmacokinetic (PK) properties that enables therapeutic efficacy with intermittent administration. This review highlights a comprehensive spectrum of ELP fusions shown to stabilize the solubility, and sometimes bioactivity, of their cargo – with a focus on biophysical properties that underlie their therapeutic effects.



中文翻译:

使用类弹性蛋白多肽实现生物活性纳米粒子的空间稳定

类弹性蛋白多肽 (ELP) 是一种多功能的热响应性聚合物,几乎可以与任何治疗药物结合。某些 ELP 源自短氨基酸序列,在人体中含量丰富,因此表现出低免疫原性。ELP 是内源性蛋白酶的底物,可生物降解,因此是候选生物材料。肽和蛋白质可以通过基因工程直接与ELP偶联,而其他聚合物和小分子可以通过共价生物共轭或非共价络合来附加。在生理温度下发生相分离的 ELP 可形成纳米组件的核心;然而,保持可溶性的 ELP 可以在空间上稳定各种纳米粒子的电晕。电晕上带有 ELP 的纳米颗粒可促进胶体具有良好的药代动力学 (PK) 特性,从而实现间歇给药的治疗效果。这篇综述重点介绍了一系列 ELP 融合物,这些融合物被证明可以稳定其货物的溶解度,有时甚至是生物活性,重点关注其治疗效果背后的生物物理特性。

更新日期:2024-01-28
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