Surface Modification Strategies and Emerging Biomedical Applications of Gold Nanoparticles

By AZoNano Staff Writers

Topics Covered

Introduction
Surface Modification Strategies
     Coating of BRMs onto Gold Nanoparticles
     Pegylated Gold Nanoparticles
     Heterogeneous Surface Design
Applications of Functionalized Gold Nanoparticles
     Nanotoxicology
     Cellular Probes
     In Vivo Cancer Application
     DNA Sensors
Conclusion
About Cytodiagnostics

Introduction

Gold nanoparticles have been used in many applications in medicine and biology, including as optical contrast agents, drug delivery vehicles, cellular probes, and biosensors. In many applications, it is necessary to modify the gold nanoparticle surface in order to make their properties suitable.

For example, modifying the nanoparticles' surface with polymers like polyethylene glycol (PEG) and polyethylene oxides minimize non-specific binding, molecules like biotin and peptides can provide gold nanoparticles specificity toward cellular targets in vitro and in vivo, and DNA makes them suitable for genetic detection.

Molecules containing oxygen, nitrogen and sulphur atoms have high binding affinity to gold atoms. Hence, the adsorption of thiolated DNA and proteins onto the gold nanoparticle surface is relatively easy.

Cytodiagnostics gold nanoparticles are designed to be ideal for adsorption coating of polymers or bio-recognition molecules (BRMs) on their surface, either by using biological interactions or by covalent conjugation, providing users more options in the design of their nanoparticle systems.

This article covers the current modification strategies and some of the emerging biomedical applications of gold nanoparticles.

Surface Modification Strategies

Coating of BRMs onto Gold Nanoparticles

Surface modification is essential to allow gold nanoparticles to recognize specific biological targets. Single-stranded DNA oligonucleotides are capable of identifying a complementary sequence, while peptides can recognize antibodies and antibodies recognize antigens. Hence, coating gold nanoparticles with these BRMs enables the particles to recognize specific targets on/in cells, in solution, or within animal tissues.

Coating of these BRMs onto the gold nanoparticle surface can typically be performed through direction adsorption or by covalent conjugation to the gold nanoparticle surface consisting of amine or carboxylic acid functional groups.

Pegylated Gold Nanoparticles

PEG is a polyether molecule that can be functionalized with alcohols, carboxylic acids, amines and thiols. The PEG molecules attach to the gold nanoparticle surface through a sulfur-gold atom bond. However, coating a thick PEG layer onto the gold nanoparticle surface can cause a reduction in non-specific binding of proteins. It was recently demonstrated that gold nanoparticles with more than 0.96 PEG/nm2 is needed to decrease non-specific binding and to hinder their uptake into macrophage cells.

Based on these results, Cytodiagnostics designed its PEGylated gold nanoparticles to have the lowest possible non-specific cellular uptake. This is a crucial quality when employing gold nanoparticles in biology, where they are programmed for targeting specific molecules or cellular receptors - reducing non-specific protein binding helps achieve the particles' high specificity.

Furthermore, Cytodiagnostics’ gold nanoparticle-PEG system consists of protruding amines or carboxylic acid functional groups, thus enabling conjugation of other molecules to the surface utilizing the coupling agent, 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC).

This reaction involves incubation of the gold nanoparticles with the biological molecules of interest and EDC for 2hr, followed by removing excess biological molecules through centrifugation. The resulting gold nanoparticle conjugates are ready for biological applications.

Heterogeneous Surface Design

Gold nanoparticles with a surface engineered to consist of PEG and BRMs can be ideally suited to their intended purpose. The bio-recognition molecule offers biological specificity, while the PEG molecule avoids non-specific binding. Cytodiagnostics gold nanoparticle products allow scientists to engineer their nanoparticles in this way to get optimum biological use.

Applications of Functionalized Gold Nanoparticles

Nanotoxicology

Understanding the impact of the physico-chemical properties of nanoparticles, their distribution in the cell and body, and the role of specific nanomaterial designs in nanotoxicity is the subject of intense research.

Gold nanoparticles are suitable platforms to conduct these analyses, on as their production can be tuned to a precise size distribution, and they readily enable designs with different shapes and surface chemistries.

These qualities make them to be evaluated systematically to gain insights into their behavior in biological systems. This enables the determination of the designs with the lowest toxicity, and their subsequent selection for the final applications.

Cellular Probes

Gold nanoparticles appear as bright spots when they are imaged using a dark field microscope due to their ability to scatter light. Hence, cells can be easily targeted and imaged by labeling gold nanoparticles with BRMs to a cell surface receptor, for instance.

Additionally, it is possible to improve low-level target detection by utilizing silver enhancement of bound gold nanoparticles.

In Vivo Cancer Application

The gold nanoparticle PEG/BRM system can be engineered to selectively target and bind to cancerous cells. A passive mechanism alone is adequate for PEGylated gold nanoparticles to target tumors.

The protective PEG-layer on the gold nanoparticles has proven to minimize non-specific macrophage uptake, thus increasing the chance of tumor extravasation by allowing the long-term stay of the nanoparticles in the blood.

Coating gold nanoparticles with a drug or imaging agent enables them to be used as a visualization tool and as a delivery vehicle to the tumor. Coating gold nanoparticles with a BRM that recognizes receptors on tumor cells is another approach of targeting tumors, called active targeting. The use of gold nanoparticles enables controlling the delivery efficiency by their shape, size and surface chemistry.

DNA Sensors

Coating of single-stranded DNA onto gold nanoparticles enables detection of genetic material. Heating the sample allows detection of mutations. DNA de-hybridizes during heating and the presence of a mutation in the sequence lowers the melting temperature. The measurement and comparison of the temperature of a mutated sequence against a perfectly complementary sequence can confirm the presence of a mutation. Cytodiagnostics provides conjugation of oligonucleotides as a cost-efficient custom service.

Conclusion

The surface of nanoparticles is their interface with the environment, and the ability to modify the surface is crucial for their use. This article covered a product with a PEGylated surface that minimizes non-specific binding to the gold surface. Further functionalization of gold nanoparticles with BRMs yields a simple yet robust strategy to target and image cellular targets and intracellular processes.

About Cytodiagnostics

Cytodiagnostics is a biotechnology company based in Burlington, Ontario, Canada. We focus on providing and developing nanotechnology derived products and services for the international life science market. Our goal is to serve our customers with the highest quality products to ensure success in their research and development efforts.

This information has been sourced, reviewed and adapted from materials provided by Cytodiagnostics.

For more information on this source, please visit Cytodiagnostics.

Date Added: Feb 27, 2014 | Updated: Mar 4, 2014
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