Amphiphilic Polyphenylene Dendron Conjugates for Surface Remodeling of Adenovirus 5.

Jessica Wagner,Volker Mailänder,Johanna Simon,Klaus Müllen,Lea Krutzke,David Y W Ng,Yuzhou Wu,Longjie Li,Tanja Weil,Katharina Landfester

doi:10.1002/anie.201913708

Abstract

Amphiphilic surface groups play an important role in many biological processes. The synthesis of amphiphilic polyphenylene dendrimer branches (dendrons), providing alternating hydrophilic and lipophilic surface groups and one reactive ethynyl group at the core is reported. The amphiphilic surface groups serve as biorecognition units that bind to the surface of adenovirus 5 (Ad5), which is a common vector in gene therapy. The Ad5/dendron complexes showed high gene transduction efficiencies in coxsackie‐adenovirus receptor (CAR)‐negative cells. Moreover, the dendrons offer incorporation of new functions at the dendron core by in situ post‐modifications, even when bound to the Ad5 surface. Surfaces coated with these dendrons were analyzed for their blood‐protein binding capacity, which is essential to predict their performance in the blood stream. A new platform for introducing bioactive groups to the Ad5 surface without chemically modifying the virus particles is provided.

Highlights

Amphiphilicity plays an important role in the formation of biological architectures such as the structure of proteins, the self-assembly of peptides, or the build-up of biological membranes.[1]
The amphiphilic surface groups serve as biorecognition units that bind to the surface of adenovirus 5 (Ad5), which is a common vector in gene therapy
Ad5 is a common vector in gene therapy but its clinical usage has limitations because of the mistargeting of plasmaprotein-coated Ad5 and acute toxicity

Summary

Introduction

Amphiphilicity plays an important role in the formation of biological architectures such as the structure of proteins, the self-assembly of peptides, or the build-up of biological membranes.[1]. The exposure of nanomaterials like polymers, liposomes, or nanoparticles to biological fluids, such as human blood plasma, gives rise to a protein corona around nanoparticles that directs their transport in vivo.[3] It has been demonstrated that either the variation of surface charges[4] or coating of nanoparticles, for example, with polymers like polyethylene glycol,[5] has an impact on the protein corona and often controls their aggregation[6] and biodistribution,[7] as well as cellular uptake properties.[5] By employing amphiphilic surface patterns on nanoparticles, their influence on biological systems was studied.[8] It is still very challenging to control the surface contour of nanoparticles[8b] and to impart distinct amphiphilic surface patterns with molecular precision that maintains their perfect nanosize definition in various biological environments.[9] highly branched macromolecules with precise structures and molecular weights, such as dendrimers, have emerged as a monodisperse platform providing characteristic features of proteins.[10] they are often referred to as “artificial proteins”[11] and their applications in biomedicine range from drug delivery of serum albumin mimicking polyphenylene dendrimers[12] to multivalent dendrimers as antiviral drugs[13] and gene delivery agents.[14] For example, it has been demonstrated that dendrons bind to a virus capsid by supramolecular interactions, leading to an electrostatically driven self-assembly into dendron-virus complexes. We analyzed the binding of blood proteins to understand the influence of amphiphilic dendron-coated surfaces in the blood stream

Results and Discussion

Conclusion

Conflict of interest