Nanomedicine for Engineers
Lead Author(s): Piyush Koria
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This is an introductory text for those who are interested in nanomedicine and biomedical engineering. No prior knowledge of biology or biological processes is required.
Chapter 1: Nanomedicine- Definition and Application
Table of Contents:
Nanomedicine is defined as the application of nanotechnology in addressing the current issues and problems that are faced in medicine and healthcare. Nanotechnology is defined as controlling and restructuring matter at the atomic and molecular levels in the nanoscale range (1-100 nm).
Why Nanoscale Range?
The primary rationale of working at the nanoscale range is that it enables scientists to utilize the unique physical, chemical and biological properties possessed by the materials at such small dimensions. Some key properties are as follows:
1. High Surface area to Volume Ratio – This is perhaps the most useful property that comes to mind when working with materials at the nanoscale range. Essentially as one makes smaller particles while keeping the volume same it results in higher surface area to volume ratio.
For example, consider a cube that has a side of 1cm (Figure 1). It has a volume of 1 cm3 while a surface area of 6 cm2, which is about 1/8th the size of a credit card. But if we break that cube into small cubes with a side of 1mm each it will result in a total of 1000 cubes. Each of these cubes will have a surface area of 6mm2 resulting in a total surface area of 6000 mm2 or 60 cm2, which is about the size of a credit card. You can further break down the cube into cubes with side of 10 nm each resulting in a total of 1018 cubes each having a surface area of 600 nm2 resulting in a total surface area of 600x1018 nm2 or 600 m2, which is slightly bigger than a standard basketball court. Thus one can quickly see how the 1 cm cube can be broken down into cubic nanoparticles having a high total surface area.
The high surface area per volume is crucial as it ensures a greater amount of the material can come into contact with the surrounding materials thus affecting its reactivity. For example, this unique property is particularly useful for increasing the efficacy of hydrophobic drugs such as curcumin. The drug is not soluble in water and thus has very limited efficacy. However, its nano-formulated version results in a much higher efficacy because of the increased surface area thereby allowing enhanced interaction of the material with cells.
2. Quantum Effects dominate at this scale: When particles of solid material are created at the visible scale (e.g. in millimeter or centimeters) there are not many differences in these particles or the solid material. However, when the particles are created at the nanoscale range (1-100 nm) the material properties change significantly from those at larger scales. This is because at the nanoscale range quantum effects dominate the behavior and properties of particles. At this range the material properties are size dependent.
One such material property is fluorescence. Quantum dots are nanosized particles that fluoresce with different colors when excited by normal visible light (Figure 2). This is essentially because of the motion of electrons that is restricted in the quantum dot particle. Depending on the size, nanoparticles from the same material will fluoresce and emit different colors. This property finds vast application in imaging and tagging different protein molecules. Also, quantum dots are fairly stable and allow multiple colors for imaging different parts of the same cell.
3. Biological Scale: The inner workings of cells naturally occur at the nanoscale. Moreover, DNA and proteins, the key molecules that serve as building blocks and regulate every cellular process are also typically in the nanoscale range (1-10 nm). Thus, working in the nanoscale enables one to manipulate either these molecules or create a microenvironment that governs cellular behavior. For example the use of multifunctional nanoparticles for targeted cancer delivery or the use of microfabricated scaffolds to create a microenvironment for regeneration.
What is the rationale of using nanotechnology in medicine?
Nanotechnology makes everything easier
At the nanoscale certain materials exhibit different physical and chemical properties that are potentially beneficical
Nanotechnology is considered the technology of the future
Nanotechnology has revolutioninzed other fields in science and technology and thus it makes sense to apply nanotechnology in health care
Is the following statement true or false: "When bulk material is broken down into smaller particles such that the volume of the particles remains the same as the bulk material, the sum of the surface area of the smaller particles is less than the surface area of the bulk material"
Examples of Application of Nanomedicine
Below are some common examples of application of Nanomedicine. Please note that this not an exhaustive list. With the evolving field new things will always be added to this list.
DNA and proteins the molecules of life: Proteins are central molecules as they serve as building blocks and are key mediators of all cellular responses and function. The deoxyribonucleic acid (DNA) molecules contain the information and instruction of proteins to be made by cells and therefore are important. Both these molecules are in the nanoscale range. Additionally, since proteins are central to cell function and its response; researchers have used these molecules for a long time to treat diseases. Additionally, the use of DNA replication, as well as transcription can be employed to develop assays for diseases detection. Finally, antigen antibody interactions are also central to diseases detection and other sensor type applications.
Nanoparticles: The most common example of nanomedicine are nanoparticles that can be used as imaging agents, drug delivery vehicles or targeting agents. NPs due to their unique size tend to accumulate in tumors because of the leaky vasculature. Also, since NPs are the same range as proteins it enables functionalizing them with targeting and apoptotic proteins. Multifunctional nanoparticles comprising of different functional domains are very common and hold great promise in treating cancer.
Probing the cellular nanoworld: The inner workings of the cells are extremely important to understand if we are to develop treatments for diseases. Here, again nanomedicine can be employed to develop novel detection techniques as well as manipulate the cellular behavior via DNA and proteins.
Creation of cell microenvironment: Most tissues have defined organized structures to enable them to function properly. Recreation of this tissue complexity is a major goal of tissue engineering that seeks to replace lost tissue function. Also, complex tissue can be used as in vitro model system to probe important biological mechanism questions as well as test drug efficacy. Since, cells recognize features at the nanoscale range as it is the scale that is similar to them it nanotechnology enables us to create these tissues.
Molecular Self-assembly: Certain molecules can be directed to self-assemble into nano-structures by simply manipulating the external environment present in them such as temperature, pH or salt concentration. Commonly referred to as bottom up approach, molecular self-assembly allows for a tighter and better control in creating the nanostructures with the unique desired properties.
Microbes: Bacteria and viruses that infect us are all at the nanoscale range. An understanding of how these microbes infect the tissue is key to prevent infections and other diseases. Also, we can “hijack” the mechanisms used by microbes to infect cells and employ it to our benefit to introduce foreign material such as genes in the cell (Transduction, Gene therapy etc.).
Nanofabricated devices as nanosensors for diagnostics /personalized medicinal applications: Diagnostics is an important area of research in healthcare and medicine. One of the issues in disease detection is the limited amount of sample available. Also, for global health perspective it is key to miniaturize extremely bulky and expensive instrumentation to cost-effective hand held devices. The use of nano-fabrication and photo-lithography has made it possible to achieve these goals in the health care. Some examples include:
- Chips for sensing glucose amounts in blood
- Circulating Tumor cells (CTC) chip for detection of circulating tumor cells from blood
- Nano-chips for detection of bacterial infection from bodily fluids such as saliva, urine or blood etc.
State True or False: "Molecular self-assembly is a top down approach for synthesis of nano-materials.
 Image courtesy of NASA