Photocrosslinked, Tunable Protein Vesicles for Drug Delivery Applications
Photocrosslinked, Tunable Protein Vesicles for Drug Delivery Applications
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用于药物输送应用的光交联、可调蛋白囊泡
DOI：
10.1002/adhm.202001810
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发表时间：
2021
影响因子：
10
通讯作者：
Champion, Julie A.
中科院分区：
文献类型：
--
作者：
Li, Yirui;Champion, Julie A.
重组蛋白因其通过基因操作和生物相容性而具有的多功能性而成为囊泡自组装的有前途的构建模块。由热响应弹性蛋白样多肽（ELP）融合蛋白组成的囊泡在组装过程中封装货物。然而，生理环境中的囊泡稳定性仍然是生物功能应用的重大挑战。据报道，将非天然氨基酸对叠氮基苯丙氨酸掺入 ELP 结构域可以实现蛋白囊泡的光交联以及囊泡大小和膨胀的调节。囊泡的大小可以通过改变 ELP 疏水性和离子强度来调节。评估蛋白囊泡封装阿霉素并在体外双重递送阿霉素和荧光蛋白的能力，作为概念证明。由此产生的由全尺寸功能性蛋白质制成的可光交联囊泡在药物递送应用中显示出巨大的潜力，特别是对于小分子/蛋白质组合疗法或靶向疗法。
Recombinant proteins have emerged as promising building blocks for vesicle self‐assembly because of their versatility through genetic manipulation and biocompatibility. Vesicles composed of thermally responsive elastin‐like polypeptide (ELP) fusion proteins encapsulate cargo during assembly. However, vesicle stability in physiological environments remains a significant challenge for biofunctional applications. Here, incorporation of an unnatural amino acid, para‐azido phenylalanine, into the ELP domain is reported to enable photocrosslinking of protein vesicles and tuning of vesicle size and swelling. The size of the vesicles can be tuned by changing ELP hydrophobicity and ionic strength. Protein vesicles are assessed for their ability to encapsulate doxorubicin and dually deliver doxorubicin and fluorescent protein in vitro as a proof of concept. The resulting photocrosslinkable vesicles made from full‐sized, functional proteins show high potential in drug delivery applications, especially for small molecule/protein combination therapies or targeted therapies.