School of Chemical and Biomolecular Engineering, BioEngineering Program, Georgia Institute of Technology, 950 Atlantic Dr. NW, Atlanta, GA, 30332-2000, USA.
Adv Healthc Mater. 2021 Aug;10(15):e2001810. doi: 10.1002/adhm.202001810. Epub 2021 Jan 29.
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.
重组蛋白作为有前途的囊泡自组装构建模块，由于其通过遗传操作的多功能性和生物相容性而受到关注。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包封货物。然而，在生理环境中囊泡的稳定性仍然是生物功能应用的一个重大挑战。在这里，将非天然氨基酸对叠氮苯丙氨酸引入 ELP 结构域中，以实现蛋白囊泡的光交联，并调节囊泡的大小和溶胀。通过改变 ELP 的疏水性和离子强度可以调节囊泡的大小。评估了蛋白囊泡包封阿霉素的能力，并体外双重递送达莫柔比星和荧光蛋白，作为概念验证。由全尺寸功能蛋白制成的光交联囊泡具有在药物输送应用中的巨大潜力，特别是对于小分子/蛋白联合治疗或靶向治疗。
