Nanoparticles in Biology and Medicine
A brief history of firsts in nanotechnology: Nanotechnology started in 1959 when Feynman gave an after-dinner talk describing molecular machines built with atomic precision. In 1974, Taniguchi used the term "nano-technology" in a paper on ion-sputter machining. The molecular nanotechnology concept was coined by Drexler at MIT in 1977. The first technical paper on molecular engineering to manufacture with atomic precision was published in 1981, when the scanning tunneling microscope (STM) was invented. The Buckyball was discovered in 1985, and the first book on nanotechnology was published in 1986. During the same year, atomic force microscopy (AFM) was invented, and the first nanotechnology organization was formed. The first protein was engineered in 1987, and many firsts followed in nanotechnology, including the publication of the first textbook about the field in 1992, as well as the first nanomedicine book published in 1999. And it all starts with particles.
Proteins that make up the cells nanomachinery are just around 5 nanometers (nm) in size. These are the sizes of the smallest man-made nanoparticles. Their size allows them to be used as probes to study the cells’ biological processes. Typically, for biological applications, nanomaterials are selected for their optical and magnetic properties. However, nanomaterials are also applied for novel electronic, optoelectronis, and memory devices. Figure 1 illustrates the size of nanoparticles.
Some applications of nano-materials in biology and medicine are:
Fluorescent biological labels for fluorescent signaling
Drug and gene delivery
Bio detection of pathogens
Detection of proteins – Antigen detection
Probing of DNA structure
Tumor destruction via heating (hyperthermia)
Separation and purification of biological molecules and cells
Linker activated nanoparticles
MRI contrast enhancement
Molecular imaging such as computed tomography (CT), positron emission computed tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance (MRI),
Nanoparticles that usually form the core of nano-biomaterials can be composed of inorganic, polymeric materials or can be in the form of nano-vesicles surrounded by a membrane or a layer. The shapes of these particles can come in different morphologies. Furthermore, nanoparticles can be functionalized in multiple ways. Figures 3 and 4 show the graphical representation of different ways to functionalize nanoparticles. For example, as depicted in figure 3, the particles can be conjugated to different types of molecules, such as antibodies, green fluorescent protein (GFP), avidin, or streptavidin, as well as to DNA/RNA oligomers and gold particles or, as shown in Figure 4, contrast agents useful for CT/MRI imaging, radiotracers useful for PET/SPECT imaging, functionalized with drugs for targeted drug delivery or specific ligands, as well as special surfaces such as hydrophilic surfactants to enhance biocompatibility.
It is thought that nanoparticles will play an increasing role in nanomedicine in the future. Nanomedicine applies nanotechnology with the goal to improve the quality of human lives. Useful medical applications of nanoparticles include improved drug delivery, such as protein, peptide, and oligonucleotide delivery in biological systems, nanoparticles to specific targets in tumors and cancers, and nanoparticles for tissue visualization to enhance surgical techniques or to visualize tumors. It is hoped that it will become possible in the near future to design nanorobots or nanomachines that allow for the repair of damage parts of the cell.
More recently, many companies have begun to use nanotechnologies. The majority of the companies are small recent spinouts of various research institutions. Most of the companies are developing applications for the pharmaceutical industry, mainly to enhance or enable drug delivery. Other companies exploit quantum size effects in semiconductor nanocrystals to tag biomolecules or use gold nanoparticles for the labeling of various cellular parts. Cytodiagnostics, one such company, provides gold, silver, and magnetic nanoparticles with sizes ranging from 5 nm to 400 nm. These particles can be conjugated to biomolecules such as antibodies, BSA, KLH, and many others.
Biosynthesis Inc. in Lewisville, Texas offers custom conjugation of antibodies or other proteins to this type of nanoparticles. To be able to perform custom conjugations, approximately 1-2 mg of purified and lyophilized antibody (or any other protein) is required.
Services include: 1. antibody or protein sourcing, if needed; 2. conjugation of a customer protein to selected gold nanoparticles; and 3. Purification of the conjugate.
Furthermore, oligonucleotides and other molecules can be conjugated to gold nanoparticles as well. Biosynthesis provides custom conjugation of single-stranded or double-stranded oligonucleotides to gold nanoparticles with sizes ranging from 5 nm to 200 nm. Final conjugate yield depends on both sizes of the oligo and nanoparticle. For a 20 mer oligo, the loading would be 0.2-1 OD/mg nanoparticle. The smaller the particle size, the higher yield.
Services include: 1. synthesis of oligonucleotides for conjugation. The customers usually supplies the nucleotide sequence, and decides which terminal (5' or 3') will be attached to the gold surface, and Biosynthesis Inc. does the rest; 2. Conjugation of the oligonucleotide to a gold nanoparticle size of customer’s choice; 3. Purification of the conjugate.
The following table shows a list of nanomedical technologies.
Cytodiagnostics, another company, offers a unique proprietary protocol that produces particles with uniform shapes and a narrow size distribution. The gold nanoparticle surface can be modified to allow for the conjugation to molecules such as biotin and other molecules of choice. Furthermore, particles can be functionalized with carboxyl, amine, and methyl groups, among others.
Figure 5: Sizes of gold nanoparticles are illustrated.
Silver Nanoparticles are also available with core sizes of 40 nm - 100nm
Figure 6: Sizes of silver nanoparticles are illustrated.
High-quality monodisperse silver nanoparticles with a narrow size distribution (CV <15%) are available as well. Nanosilver products are ideal for a wide array of applications such as “Conjugate Development,”, “Sensor Development,”, “Molecular Imaging’,’Surface Enhance Raman Spectroscopy (SERS),”, and“Bactericidal applications.”
Figure 6: Adsorption spectrum of silver nanoparticles in different wavelengths.
The company Nanoprobes offers 1.4 nm Nanogold® particles. These are gold compounds that are not just adsorbed to proteins, like colloidal gold, but covalently reacts at specific sites under mild buffer conditions with molecules that are selected for conjugation. A well-defined product can be synthesized that can be purified chromatographically.
References F Re, R Moresco and M Masserini; Nanoparticles for neuroimaging. Journal of Physics D: Applied Physics Volume 45 Number J. Phys. D: Appl. Phys. 45
Robert A. Freitas Jr., What is nanomedicine? Nanomedicine: Nanotechnology, Biology, and Medicine 1 (2005) 2– 9 http://www.foresight.org/Nanomedicine/