Nanobody-functionalized polymersomes for tumor-vessel targeting

Targeted carrier systems (e.g., liposomes or nanoparticles) are used to specifically deliver drugs to a site of interest. Site-direction can be achieved by attachment of targeting molecules, such as peptides, DNA/RNA, or antibodies, to the surface of the carrier. Here, the formation of polymersomes with tumor-targeting potential is described. A single-domain antibody (A12) that specifically targets PlexinD1 (a transmembrane protein overexpressed in tumor vasculature) is equipped with an azide-functionality using expressed protein ligation. This azide-containing A12 can subsequently be attached to BCN-functionalized polymersomes using a strain-promoted azide alkyne cycloaddition, thereby forming polymersomes with tumor-targeting potential. The preparation of polymersomes with tumor-targeting potential is described. To this end, polymersomes are equipped with a strained cyclooctyne and a tumor targeting single-domain antibody (A12) is functionalized with an azide using expressed protein ligation (EPL). Conjugation of the two yields polymersomes with an A12-coated surface.