Oriented attachment of VNAR proteins, via site-selective modification, on PLGA-PEG nanoparticles enhances nanoconjugate performance.

João C F Nogueira,Christopher J Scott,John Steven,Andrew Porter,Michelle K Greene,Daniel A Richards,Vijay Chudasama,Alexander O Furby,Caroline Barelle

doi:10.1039/c9cc02655j

Abstract

Herein we report the construction of a nanoparticle-based drug delivery system which targets a key regulator in tumour angiogenesis. We exploit a Variable New Antigen Receptor (VNAR) domain, conjugated using site-specific chemistry, to direct poly lactic acid-co-glycolic acid-polyethylene glycol (PLGA-PEG) nanoparticles to delta like canonical Notch ligand 4 (DLL4). The importance of site-specific chemistry is demonstrated.

Highlights

We report the construction of a nanoparticle-based drug delivery system which targets a key regulator in tumour angiogenesis
We recently demonstrated the importance of controlled chemical ligation for successful nanoconjugate performance, in the context of target affinity.17a This study showed that using site-selective chemistry to conjugate Trastuzumab antibody fragments (i.e. F(ab)s) to PLGA–PEG NPs resulted in superior antigen binding when compared to using classical lysine-based approaches.17a
Is presented a novel PLGA–PEG NP–Variable New Antigen Receptor (VNAR) conjugate that targets the inhibition of endothelial sprouting and proliferation.[29]

Summary

Introduction

We report the construction of a nanoparticle-based drug delivery system which targets a key regulator in tumour angiogenesis. Oriented attachment of VNAR proteins, via site-selective modification, on PLGA–PEG nanoparticles enhances nanoconjugate performance†

Results

Conclusion