First in a series dedicated to nanotechnology, this article talks about the key role of Richard Feynman in the early story of the application of nanotechnology in medicine, and the importance of being small for treating disease. The purpose of this article is also to show that nanosized drug delivery systems have already entered routine clinical use and that Europe has been pioneering in this field.
Early History: Richard Feynman & the Nobel Prize in Physics (1965)
A key date for nanotechnology and more specifically for nanotechnology applied to medicine is the year 1959, when Richard Phillips Feynman pointed out the promise and potential of nanotechnology in his historic lecture “There’s Plenty of Room at the Bottom, An Invitation to Enter a New Field of Physics”, given at the California Institute of Technology:
When we get to the very, very small world—say circuits of seven atoms—we have a lot of new things that would happen that represent completely new opportunities for design. Atoms on a small scale behave like nothing on a large scale, for they satisfy the laws of quantum mechanics. So, as we go down and fiddle around with the atoms down there, we are working with different laws, and we can expect to do different things. We can manufacture in different ways. We can use, not just circuits, but some system involving the quantized energy levels, or the interactions of quantized spins, […]
His discussion can be considered the earliest vision of nanotechnology applied to medicine as he raised the question of the “manufacture of an object that can maneuver at the level of biological cells”.
Perhaps the greatest physicist of the second half of the twentieth century, Feynman changed the way we think about quantum mechanics, the most perplexing of all physical theories. In 1965, he shared the Nobel Prize with two colleagues, Julian Schwinger and Sin-Itiro Tomonaga “[…] for their fundamental work in quantum electrodynamics, with deep-ploughing consequences for the physics of elementary particles”. In a new biography, “Quantum Man: Richard Feynman’s Life in Science”, Lawrence M. Krauss, a fellow physicist, concentrates less on Feynman the odd character and more on the thinker.
Nanoworld: Size Matters
Nanotechnologies have created a whole new “nanoworld”. Today, we are able to generate systems, from the very simple to more elaborate ones, as illustrated by the emergence of supramolecular chemistry based on molecular recognition and self-assembly processes.
Biological systems are today the playground for nanomaterial applications with the ambition of addressing unmet needs in biology. In fact, due to their very specific small size, nanoparticles are able to interact with extremely small systems. When material size matches the size of biological entities, pathways between the two systems may be established in such a way that the nanomaterials can gain access to and even operate within cells. Indeed, controlling and manipulating things at the nanometer scale allows exploration and interaction at the cellular level with unprecedented ease.
When looking at the nanometer scale, we are dealing with objects on the order of one billionth of a meter (10-9 m). To put this size in perspective, a human hair is approximately 80,000 nm wide and a red blood cell about 7,000 nm wide. Atoms are smaller than 1 nm whereas many molecules, including some proteins, are 1 nm or larger. Generally, the sizes of nanomaterials are comparable to those of viruses, deoxyribonucleic acid (DNA), and proteins whilst still being microparticles, are comparable to cells, organelles and larger physiological structures.
The strength of nanoparticles in medicine lies in their ability to operate on the same small scale as the intimate biochemical functions involved in growth, development and ageing of the human body.
Nanomedicine: Interaction Between Nanoparticles and Cells
The field of nanomedicine covers the science and technology concerning the diagnosis, treatment and prevention of diseases and traumatic injuries. It aims to relieve humans from pain and to preserve human health using molecular tools and molecular knowledge of the human body.
A major aim of medicine has long been the early and accurate diagnosis of clinical conditions so as to provide an efficient treatment without secondary effects. With the emergence of nanotechnology, the achievement of this goal seems closer than ever. For instance, multifunctional nanoparticles as an alternative system for drug and gene delivery have great potential for cancer and neuropathology therapies.
Fortunately, there has been a surge in the number of nanomaterials suitable for drug delivery. These are either made of lipids or composed of organic polymers and inorganic nanoparticles such as liposomes, dendrimers, carbon nanoparticles, quantum dots, magnetic nanoparticles, gold nanoparticles…
These systems are exploited for therapeutic purposes to carry the drug into the body, in a controlled manner, from the site of administration to the therapeutic target. In general, nanoparticles protect drugs from degradation and enhance drug absorption by facilitating their diffusion through tissues, cells and organelles. They can also modify the pharmacokinetics and the biodistribution.
Nanoparticles are also used to improve the performance of imaging techniques used for in vivo diagnosis. Nowadays, the most straightforward applications are found in cancer therapies such as Caelyx® and Doxil®. Other very challenging fields concern infectious diseases like HIV, malaria, and nosocomial infections for which already approved drugs for clinical uses have been developed (Ambisome®). Note that traditional pharmaceutical formulations meant to treat these severe diseases generally involve compounds that are highly toxic for healthy tissues, thereby greatly restricting their use in therapy, due to the occurrence of dramatic side effects.
The possible toxic side effects of nanoparticles also need to be further investigated. In general, toxicological data specific to nanoparticles remains insufficient, due to the small number of studies, the short exposure period, the different compositions of the nanoparticles tested, and the often unusual exposure route in the work environment, among other factors. Additional studies (absorption, biopersistence, etc.) are necessary to access the risk associated with inhalation exposure and percutaneous exposure.
To conclude, the development of novel materials and devices operating at the nanoscale, such as nanoparticles, provides new and powerful tools for imaging, diagnosis and therapy.
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Find Out More:
1) "Richard Feynman, the Thinker" by George Johnson. The New York Times. Published April 1, 2011
2) "IJN’s second year is now a part of nanomedicine history!" by Thomas J. Webster. Neuropsychiatric Disease and Treatment 2007:2 (1):1-2
3) Sahoo SK, Parveen S, Panda JJ. The present and future of nanotechnology in human health care. Nanomedicine 2007;3(1):20-31
4) Sanvicens N, Marco MP. Multifunctional nanoparticles-properties and prospects for their use in human medicine. Trends Biotechnol 2008;26(8):425-33