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

Adam Leach, Peter Smyth, Laura Ferguson, John Steven, Michelle K Greene, Cristina M Branco, Aidan P McCann, Andrew Porter, Caroline J Barelle, Christopher J Scott

Research output: Contribution to journalArticle

10 Downloads (Pure)

Abstract

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

Original languageEnglish
Pages (from-to)14751-14763
Number of pages13
JournalNanoscale
Volume12
Issue number27
DOIs
Publication statusPublished - 21 Jul 2020

Fingerprint Dive into the research topics of 'Anti-DLL4 VNAR targeted nanoparticles for targeting of both tumour and tumour associated vasculature'. Together they form a unique fingerprint.

  • Cite this