Photocrosslinked, Tunable Protein Vesicles for Drug Delivery Applications

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.