Bradley Duncan

Gold nanoparticle platforms as drug and biomacromolecule delivery systems

Gold nanoparticles (AuNPs) are a suitable platform for development of efficient delivery systems. AuNPs can be easily synthesized, functionalized, and are biocompatible. The tunability of the AuNP monolayer allows for complete control of surface properties for targeting and stability/release using these nanocarriers. This review will discuss several delivery strategies utilizing AuNPs.

The Interplay of Size and Surface Functionality on the Cellular Uptake of Sub-10 nm Gold Nanoparticles

Correlation of the surface physicochemical properties of nanoparticles with their interactions with biosystems provides key foundational data for nanomedicine. We report here the systematic synthesis of 2, 4, and 6 nm core gold nanoparticles (AuNP) featuring neutral (zwitterionic), anionic, and cationic headgroups. The cellular internalization of these AuNPs was quantified, providing a parametric evaluation of charge and size effects. Contrasting behavior was observed with these systems: with zwitterionic and anionic particles, uptake decreased with increasing AuNP size, whereas with cationic particles, uptake increased with increasing particle size. Through mechanistic studies of the uptake process, we can attribute these opposing trends to a surface-dictated shift in uptake pathways. Zwitterionic NPs are primarily internalized through passive diffusion, while the internalization of cationic and anionic NPs is dominated by multiple endocytic pathways. Our study demonstrates that size and surface charge interact in an interrelated fashion to modulate nanoparticle uptake into cells, providing an engineering tool for designing nanomaterials for specific biological applications.

Beauty is Skin Deep: A Surface Monolayer Perspective on Nanoparticle Interactions with Cells and Bio-macromolecules

Surface recognition of biosystems is a critical component in the development of novel biosensors and delivery vehicles, and for the therapeutic regulation of biological processes. Monolayer-protected nanoparticles present a highly versatile scaffold for selective interaction with bio-macromolecules and cells. Through the engineering of the monolayer surface, nanoparticles can be tailored for surface recognition of biomolecules and cells. This review highlights recent progress in nanoparticle-bio-macromolecule/cellular interactions, emphasizing the effect of the surface monolayer structure on the interactions with proteins, DNA, and cell surfaces. The extension of these tailored interactions to hybrid nanomaterials, biosensing platforms, and delivery vehicles is also discussed.

Nanoparticle-Stabilized Capsules for the Treatment of Bacterial Biofilms.

Bacterial biofilms are widely associated with persistent infections. High resistance to conventional antibiotics and prevalent virulence makes eliminating these bacterial communities challenging therapeutic targets. We describe here the fabrication of a nanoparticle-stabilized capsule with a multicomponent core for the treatment of biofilms. The peppermint oil and cinnamaldehyde combination that comprises the core of the capsules act as potent antimicrobial agents. An in situ reaction at the oil/water interface between the nanoparticles and cinnamaldehyde structurally augments the capsules to efficiently deliver the essential oil payloads, effectively eradicating biofilms of clinically isolated pathogenic bacteria strains. In contrast to their antimicrobial action, the capsules selectively promoted fibroblast proliferation in a mixed bacteria/mammalian cell system making them promising for wound healing applications.

Direct Cytosolic Delivery of siRNA Using Nanoparticle‐Stabilized Nanocapsules

The use of nanoparticle-stabilized nanocapsules (NPSCs) for the direct cytosolic delivery of siRNA is reported. In this approach, siRNA is complexed with cationic arginine-functionalized gold nanoparticles by electrostatic interactions, with the resulting ensemble self-assembled onto the surface of fatty acid nanodroplets to form a NPSC/siRNA nanocomplex. The complex rapidly delivers siRNA into the cytosol through membrane fusion, a mechanism supported by cellular uptake studies. Using destabilized green fluorescent protein (deGFP) as a target, 90% knockdown was observed in HEK293 cells. Moreover, the delivery of siRNA targeting polo-like kinase 1 (siPLK1) efficiently silenced PLK1 expression in cancer cells with concomitant cytotoxicity.

Co-delivery of protein and small molecule therapeutics using nanoparticle-stabilized nanocapsules.

Combination therapy employing proteins and small molecules provides access to synergistic treatment strategies. Co-delivery of these two payloads is challenging due to the divergent physicochemical properties of small molecule and protein cargos. Nanoparticle-stabilized nanocapsules (NPSCs) are promising for combination treatment strategies since they have the potential to deliver small molecule drugs and proteins simultaneously into the cytosol. In this study, we loaded paclitaxel into the hydrophobic core of the NPSC and self-assembled caspase-3 and nanoparticles on the capsule surface. The resulting combination NPSCs showed higher cytotoxicity than either of the single agent NPSCs, with synergistic action established using combination index values.

Immobilization and Stabilization of Lipase (CaLB) through Hierarchical Interfacial Assembly

Nanostructure-enabled hierarchical assembly holds promise for efficient biocatalyst immobilization for improved stability in bioprocessing. In this work we demonstrate the use of a hierarchical assembly immobilization strategy to enhance the physicochemical properties and stability of lipase B from Candida antarctica (CaLB). CaLB was complexed with iron oxide nanoparticles followed by interfacial assembly at the surface of an oil-in-water emulsion. Subsequent ring opening polymerization of the oil provided cross-linked microparticles that displayed an increase in catalytic efficiency when compared to the native enzyme and Novozym 435. The hierarchical immobilized enzyme assembly showed no leakage from the support in 50% acetonitrile and could be magnetically recovered across five cycles. Immobilized lipase exhibited enhanced thermal and pH stability, providing 72% activity retention after 24 h at 50 °C (pH 7.0) and 62% activity retention after 24 h at pH 3.0 (30 °C); conditions resulting in complete deactivation of the native lipase.

Detection of bacteria using inkjet-printed enzymatic test strips.

Low-cost diagnostics for drinking water contamination have the potential to save millions of lives. We report a method that uses inkjet printing to copattern an enzyme–nanoparticle sensor and substrate on a paper-based test strip for rapid detection of bacteria. A colorimetric response is generated on the paper substrate that allows visual detection of contamination without the need for expensive instrumentation. These strips demonstrate a viable nanomanufacturing strategy for low-cost bacterial detection.

Rapid Coating of Surfaces with Functionalized Nanoparticles for Regulation of Cell Behavior

A robust monolayer of nanoparticles is formed via dip-coating of cell culture plates. These surfaces provide cell type-specific modulation of growth behavior without the uptake of nanoparticles.

A Multichannel Biosensor for Rapid Determination of Cell Surface Glycomic Signatures.

Cell surface glycosylation serves a fundamental role in dictating cell and tissue behavior. Cell surface glycomes differ significantly, presenting viable biomarkers for identifying cell types and their states. Glycoprofiling is a challenging task, however, due to the complexity of the constituent glycans. We report here a rapid and effective sensor for surface-based cell differentiation that uses a three-channel sensor produced by noncovalent conjugation of a functionalized gold nanoparticle (AuNP) and fluorescent proteins. Wild-type and glycomutant mammalian cells were effectively stratified using fluorescence signatures obtained from a single sensor element. Blinded unknowns generated from the tested cell types were identified with high accuracy (44 out of 48 samples), validating the robustness of the multichannel sensor. Notably, this selectivity-based high-throughput sensor differentiated between cells, employing a nondestructive protocol that required only a single well of a microplate for detection.