A closer look at nanomedicine

(Nanowerk Spotlight) In our May 7 spotlight "The potential and the pitfalls of nanomedicine" we took a general look at the potential implications of nanomedicine and addressed some ethical issues that arise as the technology develops. In part two of this article we now take a closer look at emerging nanomedical techniques such as nanosurgery, tissue engineering, nanoparticle-enabled diagnostics, and targeted drug delivery. Again, the ethical issues inherent in these emerging medical technologies need to be considered. There are established principals for ethical assessment of existing, conventional, medical technologies and a new research article examines if and how these principals can be extended to nanomedicine."We show that even though ethical problems in nanomedicine may be more complex than ethical problems in medicine and biotechnology in general, for example the toxicity of nanoparticles resulting from their nanoscale size, fundamentally the same general ethical principles are at stake, such as respect for autonomy, beneficence, nonmaleficence, and justice" Mette Ebbesen and Dr. Thomas G. Jensen explain in their recent article "Nanomedicine: Techniques, Potentials, and Ethical Implications"."These ethical principles have been used for ethical assessment in biomedicine for years, and they form part of several different ethical theories, including the bioethical theory of Beauchamp and Childress ("Principles of Biomedical Ethics"). This means that even though nanomedicine raises concrete ethical issues that are more complex than those raised by existing technology, a reasonably sound knowledge base has already been acquired in the field of bioethics that can be extended to nanomedicine."Ebbesen is a researcher at the Department of Systematic Theology and Jensen is a professor at the Institut for Human Genetik, both at Aarhus University in Denmark.Nanotechnology promises us a radically different medicine than the cut, poke and carpet bomb (think chemotherapy) medicine of today. The two major differences of nanomedicine will be a) the tools it uses – the main workhorse will be multifunctional nanoparticles (see Nanowerk Spotlight "Creating the nanotechnology wunderkind in pharmaceutics: multifunctional nanocarriers") – and b) it will enable a perfectly targeted and individual treatment: organs and bones, really any body tissue, can be diagnosed and treated on a cell by cell basis with precise dosing and monitoring through the use of biomolecular sensors. In their paper, the authors focus on three particular areas where nanotechnology will revolutionize medicine:NanosurgeryRobert A. Freitas Jr. describes the early forms of cellular nanosurgery that are being explored today using pipettes, atomic force microscopes (AFM) and femtolasers: "For example, a rapidly vibrating (100 Hz) micropipette with a <1 micron tip diameter has been used to completely cut dendrites from single neurons without damaging cell viability. Axotomy of roundworm neurons was performed by femtosecond laser surgery, after which the axons functionally regenerated. A femtolaser acts like a pair of “nano-scissors” by vaporizing tissue locally while leaving adjacent tissue unharmed. Femtolaser surgery has performed: (1) localized nanosurgical ablation of focal adhesions adjoining live mammalian epithelial cells, (2) microtubule dissection inside yeast cells, (3) noninvasive intra tissue nanodissection of plant cell walls and selective destruction of intracellular single plastids or selected parts of them, and even (4) the nanosurgery of individual chromosomes (selectively knocking out genomic nanometer-sized regions within the nucleus of living Chinese hamster ovary cells). These procedures don’t kill the cells upon which the nanosurgery was performed. AFM have also been used for bacterium cell wall dissection in situ in aqueous solution, with 26 nm thick twisted strands revealed inside the cell wall after mechanically peeling back large patches of the outer cell wall."Looking into the future, Freitas envisions "biocompatible surgical nanorobots that can find and eliminate isolated cancerous cells, remove microvascular obstructions and recondition vascular endothelial cells, perform “noninvasive” tissue and organ transplants, conduct molecular repairs on traumatized extracellular and intracellular structures, and even exchange new whole chromosomes for old ones inside individual living human cells."More near-term applications of AFM and femtolaser nanosurgery most likely will include cell therapy, eye surgery, and neurosurgery, tissue engineering, laser-assisted in vitro fertilization (IVF), and gene therapy.Ebbesen and Jensen argue that there appear to be numerous advantages of nanosurgery techniques compared with existing, mostly microscale, surgical procedures. Therefore the risk-benefit ratio of nanosurgery techniques are likely to be smaller than the risk-benefit ratio of already established microsurgery techniques. However, they caution that the exact risk benefit ratios need to be based on detailed experiments.The ethics issue becomes more complicated if nanosurgery techniques in the future are to be used for gene therapy and the enhancement of human capabilities. Germline therapy (where the genetic changes will not only affect the patient but also his/her offspring; this is in contrast to somatic cell therapy that only affects the treated patient) is not allowed in many countries; for instance, its forbidden under the EUConvention on Human Rights and Biomedicine. By potentially making this kind of therapy easier to perform, these nanosurgery procedures are likely to lead to a renewed debate. Of course this is a double-edged sword: one one hand, opponents argue that experiments with germline therapy could be seen as tantamount to a clinical experiment on unconsenting subjects, who are the affected members of future generations. On the other hand, proponents say that human rights should not be interpreted as imposing on us morally unsustainable obligations, such as the obligation to abstain from curing people.While the medical applications of nanosurgery could be seen as just advanced techniques of restoring and maintaining human health, an entirely possible scenario could be the creation of superhuman capabilities (so-called transhumans). The issues go beyond what's already being discussed in the context of gene therapy because future surgical procedures could involve the implantation of nanoscale sensors and chips that would enhance existing human capabilities, for instance being able to see in the dark thanks to implanted ultrasound sensors.This raises a large number of issues – already familiar from the debate on gene therapy – ranging from moral aspects (e.g., should parents be allowed to "engineer" their children?) and equality issues (e.g., who should be offered the enhancement treatments - only people who could afford them?) to global societal implications (do industrialized nations have a responsibility to make these technologies available to developing countries?).Tissue engineeringNanotechnology-enabled tissue engineering is receiving increasing attention. The ultimate goal of tissue engineering as a medical treatment concept is to replace or restore the anatomic structure and function of damaged, injured, or missing tissue. At the core of tissue engineering is the construction of three-dimensional scaffolds out of biomaterials to provide mechanical support and guide cell growth into new tissues or organs (see our Nanowerk Spotlight "One day doctors will grow new bones with nanotechnology"). Experimental efforts are currently underway for tissue engineering involving virtually every type of tissue and every organ of the human body.Ebbesen and Jensen point out that ethical analysis of tissue engineering in general requires a risk analysis similar to that required in relation to nanosurgery, and informed consent should be obtained from both the cell-donor and the participant in the clinical trial. They caution that the use of embryonic stem cells for tissue engineering and therapeutic cloning raises some specific ethical issues going beyond 'simple' tissue engineering. The ongoing debate on stem cell research reflects these issues.Nanoparticle-enabled diagnostics and drug deliveryFrom an ethical point of view perhaps the least contentious are of nanomedicine involves nanoparticulate diagnostic and drug delivery methods. Having said that, the potential toxicity of engineered nanoparticles is an unsolved issue and still needs to be dealt with.There are numerous engineered constructs, assemblies, architectures and particulate systems used for diagnostics and targeted drug delivery, whose unifying feature is their nanoscale size range. These include polymeric micelles, dendrimers, polymeric and ceramic nanoparticles, protein cage architectures, viral-derived capsid nanoparticles, polyplexes, and liposomes (as an example, see our Nanowerk Spotlight"Nanocarriers could become an alternative to brain surgery ").Throughout their discussion, Ebbesen and Jensen follow the bioethical theory of Beauchamp and Childress, mentioned above, because the principles of their theory (respect for autonomy, beneficence, nonmaleficence, and justice) find support across different cultures. The authors state, however, that "even though these principles are generally acknowledged, this does not mean that there is consensus about what is good and bad. Interesting debates occur when the principles are to be interpreted and balanced in specific historical, social, economic, and political contexts."The authors conclude: "The analysis of potential ethical problems in nanomedicine shows that even though ethical questions in nanomedicine may be more complex than ethical questions in general medicine and biotechnology, for example the toxicity of nanoparticles resulting from their nanoscale size, fundamentally the same general ethical principles, such as respect for autonomy, beneficence, nonmaleficence, and justice, are at stake."That means that, even though nanomedicine raises ethical issues that are more complex than those raised by existing technology, a reasonably sound knowledge base has already been acquired in the field of bioethics that can be extended to nanomedicine.

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