Insights into the interfacial structure–function of poly(ethylene glycol)-decorated peptide-stabilised nanoscale emulsions

Abstract

The interfacial properties of nanoscale materials have profound influence on biodistribution and stability as well as the effectiveness of sophisticated surface-encoded properties such as active targeting to cell surface receptors. Tailorable nanocarrier emulsions (TNEs) are a novel class of oil-in-water emulsions stabilised by molecularly-engineered biosurfactants that permit single-pot stepwise surface modification with related polypeptides that may be chemically conjugated or genetically fused to biofunctional moieties. We have probed the structure and function of poly(ethylene glycol) (PEG) used to decorate TNEs in this way. The molecular weight of PEG decorating TNEs has considerable impact on the ζ-potential of the emulsion particles, related to differential interfacial thickness of the PEG layer as determined by X-ray reflectometry. By co-modifying TNEs with an antibody fragment, we show that the molecular weight and density of PEG governs the competing parameters of accessibility of the targeting moiety and of shielding the interface from non-specific interactions with the environment. The fundamental understanding of the molecular details of the PEG layer that we present provides valuable insights into the structure-function relationship for soft nanomaterial interfaces. This work therefore paves the way for further rational design of TNEs and other nanocarriers that must interact with their environment in controlled and predictable ways.

Controlling nanoemulsion surface chemistry with poly(2-oxazoline) amphiphiles

“…[1][2][3][4] For biomedical applications, the advantageous safety and clearance properties of so organic materials have propelled liposomes, polymer micelles, hydrogels, and dendrimers into the research spotlight. [5][6][7][8][9][10] Surprisingly, far less attention has been placed on incorporating chemical complexity into emulsions [11][12][13] despite their simple formation and ability to encapsulate signicant amounts of cargo. [14][15][16] Emulsions are liquid-in-liquid droplets stabilized by surfactant, with size distributions ranging from several nanometers to hundreds of micrometers.…”

“…36,37 Furthermore, chemically robust approaches to append functionality to the surface of emulsions are limited in comparison to conventional nanoparticles. 12,13,35,38,39 Surfactants play Fig. 1 (A) Surfactants dictate the size, charge, and surface chemistry of emulsions.…”

“…Conventional emulsion surface functionalization techniques involve modication of the surfactant prior to emulsication. 13,[49][50][51] The functionalized surfactant can be employed solely or in combination with other surfactants. Limitations to this approach are the reliance on cosurfactants 52 and the inability to decouple size and surface charge.…”

Refining nanocarrier emulsions for pharmaceutical use

“…Active targeting of NEs can be achieved by surface modification with targeting ligands, such as antibodies (Ansell et al, 2000), aptamers (Wu et al, 2015, Aaldering et al, 2015 and small molecules (Kue et al, 2016) (Milane et al, 2010). Targeting moieties that can be conjugated to NEs to target a specific antigenic site include vitamins, aptamers, sugars, peptides, antibodies and synthetic polymers, (Zeng et al, 2013, Tayeb et al, 2017, Talekar et al, 2012, Mulik et al, 2010. Monoclonal antibodies and their derived fragments are commonly used for active tumour targeting due to their exquisite specificity, high affinity and, in the case of Fab fragments and scFv antibodies, their small size (Ahmad et al, 2012).…”

“…Recently, a novel peptide-stabilised NE system has been developed that decouples emulsification from controlled surface modification. Characterised by the spontaneous and step-wise addition of functional moieties linked to a designer protein biosurfactant (Zeng et al, 2013), this platform allows the rational generation of sophisticated interfaces (Tayeb et al, 2017).…”