Tailoring dendritic biohybrids as defined protein nanotransporters

Abstract

Biohybrid materials involving the chemical fusion of biomolecules with synthetic entities have received significant focus as these conjugates display unique bio-synthetic synergy.

In this dissertation, we explore the use of dendrons (defined dendrimer segments) taking on the role as the synthetic element and proteins being the biological component as they share very similar physical characteristics (globular and monodispersed), yet vastly different chemical behaviour. From the design of the dendrons, we show the various chemistry involved in selecting the suitable dendritic scaffold as well as a strong emphasis in the conjugation techniques for the macromolecular construction of the dendritic biohybrid and their implications on the biological system.

Three major strategies (covalent, non-covalent and pH responsive supramolecular chemistry) were individually developed and the resultant dendritic conjugates analyzed for their potential to function as nanotransporters for molecular and protein therapeutics. Through fluorescence microscopy and cytotoxicity assays on cancer cell lines, these conjugates were shown to alleviate common problems associated with proteins (i.e. stability in plasma, membrane impermeability) and display improved pharmacokinetics. These systematically different conjugates exhibited unique properties based on their chemical design.

In perspective, these dendritic proteins have shown great engineering capacity based on chemical design and have provided a highly optimistic outlook as a contemporary class of biohybrid materials.