Nanotechnology in biomedicine

Many diseases are caused by alterations in biological processes at the molecular or nanometric level. Mutated genes, misfolded proteins, and infections caused by viruses or bacteria can produce cellular malfunction, translating into serious diseases. These molecules and infectious agents have a nanometric size and may be located in biological systems protected by nanosized barriers such as the nuclear pore with a diameter of 9 nm.

Nanotechnology is defined as the design, characterization, production and application of materials, structures, devices and systems in the nanometric range (1-100 nm).

The application of nanotechnology to medicine is changing the way we look at cancer:

Nanomedicine is aimed to use the characteristics and physical properties of nanomaterials for the diagnosis and treatment of diseases at the molecular level.

In the figure below you can see some of the most frequently used materials in nanomedicine:

Taken from Kim et al. N Engl J Med 2010

Of particular interest is the one-atom thick layer of graphite, called graphene. The Nobel Prize in Physics 2010 was awarded jointly to the Russian researchers Andre Geim and Konstantin Novoselov "for groundbreaking experiments regarding the two-dimensional material graphene". Graphene is the basic structural element of carbon nanotubes. Below, you can see a video showing how the medical applications of graphene could be in the future:

MEDICAL APPLICATIONS OF NANOTECHNOLOGY

Nanodiagnosis: the diagnosis of some diseases can be improved by using nanoparticles that interact with the molecules related to the disease present in the blood, body fluids or tissues.

Drug release: nanotechnology may be more effective in drug delivery and reaching the target tissue than conventional systems.

Some aspects of the application of nanotechnology in the diagnosis and treatment of cancer can be seen in the following video:

Nanotechnology has also potential in regenerative medicine, particularly in the diagnosis and management of cardiovascular diseases, in the development of prosthesis and in the creation of artificial retina.

Other fields where nanotechnology could have application are: treatment of infectious diseases, nanosurgery and odontology.

In the following video a technique using nanoparticles aimed to reduce the toxicity of radiotherapy and improve the effectivity of the treatment is explained: 

The use of nanoparticules raises novel and important ethical concerns regarding mainly the potential toxic side effects in the body and the potential ecological impact on the environment.

Familiarize yourself with the following concepts:

• Definition of nanotechnology
• Principal nanomaterials
• Applications in biomedicine
• Advantages and disadvantages of nanotechnology
• Main ethical concerns

Basic molecular biology in biomedical research

Milestones of molecular biology

The major advances in genetic engineering have occured during the last 6 decades, but the history of molecular biology started at the end of the XIX century with the research of Darwin and Mendel. On his book "On The Origin of Species", Charles Darwin explained that heredity is the mechanism that perpetuates variations, since the traits in offspring result from a blending of the traits of each parent. The Austrian friar Gregor Mendel conceived the idea of heredity units, which he called "factors" (later known as "genes"), by studying Pisum sativum, or the common pea plant. Mendel proposed that "factors" normally occur in pairs and these two "particles" of the factors (later known as "alleles") segregate from each other in the formation of gametes. Therefore, Mendel stated that each individual inherits two "particles" for each trait, one from each parent.  In 1869, Friedrich Miescher first isolated what he called "nuclein" (later known as "deoxyribonucleic acid" or "DNA" inside the nuclei of human white blood cells. 

 

In 1953, Dr. James Watson and Dr. Francis Crick deduced the three dimensional, double-helical model for the structure of DNA, based on some crucially important X-ray chrystallography work of Dr. Rosalind Franklin and Dr. Maurice Wilkins. Watson, Crick and Wilkins received the Nobel Prize in Medicine for the double-helix model of DNA in 1962, but the scientific work of Rosalind Franklin was not recognized. The picture on the right pannel illustrates the schematic respresentation of the double-helix model of DNA proposed by Watson and Crick and published in the prestigious Nature journal (view the manuscript here).

In 1990 the second major milestone in the genetics of the XX century started with the sequentiation of the human genome in the "Human Genome Project", that concluded in 2003. A working draft of the Human Genome was completed and simultaneously published in Nature and Science on February 15, 2001.

New challenge in molecular biology: the ENCODE project

ENCODE (acronym of ENCyclopedia Of DNA Elemens) is a project funded by the National Human Genome Research Institute to identify all regions of transcription, transcription factor association, chromatin structure and histone modification in the human genome sequence. Thanks to the identification of these elements, 80% of the components of the human genome now have at least one biochemical function associated with them, in particular, the non-encoding regions. In this link to the ENCODE project, the most relevant results obtained in relation to the organization and regulation of the genes are shown.

The identification of new elements of the human genome has revealed new insights into biomedical research, as you can see in this video:

The central dogma of molecular biology consists of three main processes: DNA replication, RNA transcription and protein translation. Some of the basic techniques used in biomedical research are shown below:

Molecular techniques for the study of DNA:

• Analysis of numeric chromosomal anomalies: cariotype.
• Analysis of structural chromosomal anomalies: FISH 
• Detection of mutations: RFLP.
• Study of gene function: transgenic animals.

Molecular techniques for the study of RNA:

• Conversion of RNA to cDNA: reverse transcription.
• Gene expression analysis: conventional PCR, real-time PCR and microarrays.

Molecular techniques for the study of proteins:

• Quantification of proteins: ELISA, western-blot and proteomics.
• Localization of proteins: immunohistochemistry.
•  Study of protein function: stimulation of cell cultures, inoculation in experimental animals or patients.