Gulen Yesilbag Tonga

25th Anniversary Article: Interfacing Nanoparticles and Biology: New Strategies for Biomedicine

The exterior surface of nanoparticles (NPs) dictates the behavior of these systems with the outside world. Understanding the interactions of the NP surface functionality with biosystems enables the design and fabrication of effective platforms for therapeutics, diagnostics, and imaging agents. In this review, we highlight the role of chemistry in the engineering of nanomaterials, focusing on the fundamental role played by surface chemistry in controlling the interaction of NPs with proteins and cells.

Inorganic nanosystems for therapeutic delivery: status and prospects.

Inorganic nanomaterials have an array of structural and physical properties that can be used in therapeutic delivery systems. The sizes, shapes, and surfaces of inorganic nanomaterials can be tailored to produce distinct interactions with biological systems both in vitro and in vivo. Nanoparticle cores can likewise be engineered to possess unique opticophysical properties, including upconversion, size-dependent absorbance/emission as well as magnetic properties such as superparamagnetism. These properties make inorganic nanomaterials as useful imaging agents for noninvasive diagnostics and remotely activated theragnostics. Taken together, these unique properties of inorganic nanomaterials make them promising delivery systems.

Direct Cytosolic Delivery of CRISPR/Cas9-Ribonucleoprotein for Efficient Gene Editing

Genome editing through the delivery of CRISPR/Cas9-ribonucleoprotein (Cas9-RNP) reduces unwanted gene targeting and avoids integrational mutagenesis that can occur through gene delivery strategies. Direct and efficient delivery of Cas9-RNP into the cytosol followed by translocation to the nucleus remains a challenge. Here, we report a remarkably highly efficient (∼90%) direct cytoplasmic/nuclear delivery of Cas9 protein complexed with a guide RNA (sgRNA) through the coengineering of Cas9 protein and carrier nanoparticles. This construct provides effective (∼30%) gene editing efficiency and opens up opportunities in studying genome dynamics.

Surface Charge Controls the Suborgan Biodistributions of Gold Nanoparticles

Surface chemistry plays a deciding role in nanoparticle biodistribution, yet very little is known about how surface chemistry influences the suborgan distributions of nanomaterials. Here, using quantitative imaging based on laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), we demonstrate that surface charge dictates the suborgan distributions of nanoparticles in the kidney, liver, and spleen of mice intravenously injected with functionalized gold nanoparticles. Images of the kidney show that positively charged nanoparticles accumulate extensively in the glomeruli, the initial stage in filtering for the nephron, suggesting that these nanoparticles may be filtered by the kidney at a different rate than the neutral or negatively charged nanoparticles. We find that positively and negatively charged nanoparticles accumulate extensively in the red pulp of the spleen. In contrast, uncharged nanoparticles accumulate in the white pulp and marginal zone of the spleen to a greater extent than the positively or negatively charged nanoparticles. Moreover, these uncharged nanoparticles are also more likely to be found associated with Kupffer cells in the liver. Positively charged nanoparticles accumulate extensively in liver hepatocytes, whereas negatively charged nanoparticles show a broader distribution in the liver. Together these observations suggest that neutral nanoparticles having 2 nm cores may interact with the immune system to a greater extent than charged nanoparticles, highlighting the value of determining the suborgan distributions of nanomaterials for delivery and imaging applications.

Recognition of glycosaminoglycan chemical patterns using an unbiased sensor array

A sensor array composed of eight functionalized gold nanoparticles and a fluorescent polymer was utilized to identify 11 glycosaminoglycans (GAGs) by their chemical signatures. Particle ligand structure was key in differentiating analytes, with aromatic and specific sugar functionalities recognizing GAG structural parameters including sulfonation, acetylation, epimeric structure, size, and charge.

The role of surface functionality in nanoparticle exocytosis

Getting out is just as important for nano-therapeutics as getting in. Exocytosis rates determine residency time in the cell, an important determinant for therapeutic efficacy and also for eventual clearance from the cell. In this study, it is shown that exocytosis efficiency is determined by surface functionality, providing a strategy for optimizing nanocarriers.

Photocleavable Hydrogels for Light-Triggered siRNA Release.

A photocleavable hydrogel system for on-demand delivery of genetic material is reported. The release of short interfering RNAs can be triggered by the application of UV light without any loss in bioactivity. This approach provides a promising external stimulus-based nucleic acid delivery platform for applications in disease therapeutics and tissue regeneration.

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.

Characterization of surface ligands on functionalized magnetic nanoparticles using laser desorption/ionization mass spectrometry (LDI-MS)

Functionalized magnetic nanoparticles (MNPs) have been characterized by laser desorption/ionization mass spectrometry (LDI-MS). Quantitative information about surface ligand composition and structure for monolayer and mixed monolayer protected Fe3O4 and FePt NPs can be obtained rapidly with very little sample consumption.

High Yield Synthesis of Aspect Ratio Controlled Graphenic Materials from Anthracite Coal in Supercritical Fluids

This paper rationalizes the green and scalable synthesis of graphenic materials of different aspect ratios using anthracite coal as a single source material under different supercritical environments. Single layer, monodisperse graphene oxide quantum dots (GQDs) are obtained at high yield (55 wt %) from anthracite coal in supercritical water. The obtained GQDs are ∼3 nm in lateral size and display a high fluorescence quantum yield of 28%. They show high cell viability and are readily used for imaging cancer cells. In an analogous experiment, high aspect ratio graphenic materials with ribbon-like morphology (GRs) are synthesized from the same source material in supercritical ethanol at a yield of 6.4 wt %. A thin film of GRs with 68% transparency shows a surface resistance of 9.3 kΩ/sq. This is apparently the demonstration of anthracite coal as a source for electrically conductive graphenic materials.