Nanotechnology and Oncology Workshop Summary (2011) / Chapter Skim
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4 Risks Associated with Nanotechnology
4 Risks Associated with Nanotechnology
Pages 41-52
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From page 41... ...
These barriers include the reticuloendothelial system (RES) of the immune system, the kidneys, the liver, blood vessel walls, the tumor cell membrane, the cytosol or the nuclear membrane of a tumor cell, ionic and molecular pumps within tumor cells, and enzymatic degradation.
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From page 42... ...
. The properties of nanomaterials make it difficult to predict how they will penetrate these various biological barriers or be metabolized, which in turn makes it difficult to assess their biodistribution and toxicity, several speakers noted.
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From page 43... ...
. In contrast to biological materials such as red blood cells or cancer cells, deformability has not been thoroughly explored as a characteristic impacting biodistribution and toxicity of nanomaterials.
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From page 44... ...
These studies indicate that nanoparticles with high surface charge are cytotoxic regardless of particle type, and that uncoated nanoparticles will accumulate in the liver and spleen, and they are more likely to be digested by phagocytes, unlike those that are PEGylated. "We found that some of our in vitro results, at least for optimization, do in fact mimic what we're seeing in vivo," Dr.
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From page 45... ...
45 RISKS ASSOCIATED WITH NANOTECHNOLOGY Nanomaterial synthesis Physical Interrelated characterization materials properties Shape Size Zeta potential Charge Hydrophobicity Chemical characterization Surface chemistry: Functional groups Protein interactions Biological Cytotoxicity characterization Cellular response Organ distribution Metabolic pathway Immuno-suppression/ stimulation Clearance Interrelated pharmaco kenetic properties FIGURE 8 Special ADME considerations for nanomedicine. NOTE: ADME = absorption, distribution, metabolism, excretion.
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From page 46... ...
"We need to understand surface interactions much more than we do now, as well as a variety of other aspects in order to get to that goal of being able to look at the physical and chemical properties of a nanomaterial and be able to say, ‘well here's how it's going to interact in a cell, in a biological fluid, in a sand bed, river, etc.'" So despite the emerging body of knowledge on nanotxoicity, often multiple studies are needed to characterize complex nanoparticles and show where they are likely to be distributed in the body when conducting clinical trials. Some of these studies are rather esoteric, Dr.
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From page 47... ...
She also pointed out that the International Council on Nanotechnology recently established an open-source website for sharing information about occupational practices for the safe handling of nanomaterials that they call the "GoodNanoGuide." Multiple stakeholders contribute, share, and discuss information on this site, which is modern, interactive, and up-todate.1 "We're looking at tasks that might be performed in a manufacturing or research environment and saying ‘here are the potential human exposures, and here are the potential controls that you might want to use,'" Dr. Kulinowski explained.
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From page 48... ...
Zhao and his colleagues suggested that the lung toxicity was not due to the nanoparticles, but rather due to the fumes produced by the heating of the polyacrylate esters. He called for more assessment technologies and procedures to investigate potential nanotoxicities.
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From page 49... ...
You look histologically at every possible organ, do all the blood chemistries, so if there is any particular toxicity, whether it be nanoparticle-related or not, you should be able to find it. I know it has been talked about that nanoproducts may have a different toxicology profile, but I think that the published papers, and maybe the little bit of hype in the lay press, has probably been more as a result of occupational exposure in the heavy industry settings … as opposed to the pharmaceutical applications," he said.
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From page 50... ...
"But it has heightened the issue of elimination in nanotechnology -- where do things go, how long to they stay, and can they cause toxicity years and months after they have been given." Dr. Barker noted that the safety issues raised by nanomedicines are not any different than what has been raised by biologics, and the biggest toxicity issues have not been related to long residence times of the agent in the body, but rather how these biologics alter factors that cannot be measured.
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From page 51... ...
Dr. Hawk added that lowering the toxicity of cancer prevention agents is the main goal for applying nanotechnology to the cancer prevention field.
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From page 52... ...
Dr. Duncan stressed engaging the public in risk–benefit assessments of nanotechnologies.
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