Anti-DLL4 VNAR targeted nanoparticles for targeting of both tumour and tumour associated vasculature.

摘要: Whilst there is an extensive body of preclinical nanomedicine research, translation to clinical settings has been slow. Here we present a novel approach the targeted nanoparticle (NP) concept: utilizing both targeting ligand, VNAR (Variable New Antigen Receptor), shark-derived single chain binding domain, and under-investigated target in delta-like ligand 4 (DLL4). We describe development anti-DLL4 site-specific conjugation this poly(lactic-co-glycolic) acid PEGylated NPs using surface maleimide functional groups. These nanoconjugates were shown specifically bind DLL4 with high affinity preferentially internalized by DLL4-expressing pancreatic cancer cell lines endothelial cells. Furthermore, distinct anti-angiogenic effect endowed was evident vitro tubulogenic assays. Taken together these findings highlight potential polymeric as therapeutic cancer.