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Cancer nanotechnology is a field that is centered on developing breakthroughs for cancer diagnosis and therapy. Nanotechnology has been characterizing methods to penetrate tumors using nanoscale devices with a high level of selectivity and specificity. The field of nanotechnology has also been developing new drug-delivery systems for cancer treatment. There have been many nanoscale devices that have been developed over the last few years including nanoshells, liposomes, micelles, and quantum dots. There has also been progress made with using nanotechnology for improving imaging techniques for cancer diagnostics. Nanotechnology has also played a role in target specific drug therapy for cancer. Effectively targeting tumor tissues might help improve treatment regimens by focusing treatment targeted against tumor tissue rather than healthy tissue. Due to effective targeting, therapies can be more selective and reduce drug side effects and toxicity. ,
The size of the nanoparticles allows for easy penetration through small blood vessels and also allows for easy cellular uptake. Additionally, the unique structure of tumor vasculature is an advantage to using nanoparticles for tumor penetration. Tumors contain abnormal chaotic blood vessels with poor differentiation, which enhances the permeability and as a result leads to an increased accumulation of nanoparticles within tumor tissue. Nanoparticles can be used as carriers for drug targets. Using molecules to selectively bind to receptors on uniquely expressed target tissue on tumor cells can enhance delivery of drugs. , ,
Nanodevices like liposomes, quantum dots, nanoshells have been developed for effective targeting. Active targeting involves using ligands and linking them to nanoparticles that are specifically targeted for tumors, whereas passive targeting involves using the nature of the tumor vasculature for accumulation of the nanoparticles. Lipid based devices like micelles and liposomes have been used because the particles have increased solubility, which results in limited toxicity. Quantum dots are nanocrystals that have fluorescence emission and can be designed as probes to link to DNA expressing tumor tissue. This has been useful in developing techniques to monitor cancer treatment and imaging tumor vessels in vivo as well as imaging in real time. However, there have been some limitations of the use of quantum dots because of toxicity since they are known to release toxic cadmium in response to UV light. Other devices like nanoshells have the ability to emit and absorb infrared light and are more advantageous than using quantum dots because they do not have the potential for toxicity with heavy metals like cadmium. Nanoshells can also absorb light and generate heat for tumor ablation. Nanoshells similarly can be targeted to tumor tissue and have also been attractive in its use with in vivo imaging.
Nanotechnology has also made some advances in the field of neurosurgery and has shown to be advantageous at designing drug-delivery mechanisms to the central nervous system. Nanoparticles also have shown efficacy at crossing the biophysical barriers like the blood brain barrier and can be designed to penetrate, enhance transport, and carry therapeutic agents to tumor tissue. According to the article by Orringer et al, nanoparticles have been shown to pass through blood-brain barriers and are retained in brain tumor tissue. This study importantly addresses the question of whether there is efficacy in using nanodevices to improve the ability of neurosurgeons to radiographically visualize and surgically remove brain tumors. The study used in vitro methods to analyze how nanoparticles can be loaded with dye for visualization and coated with a peptide that can bind to tumor receptors. The study showed that the nanoparticles had great affinity for glioma cells and can be used for selectively targeting glioma cells that express nucleolin on the tumor receptor.
Although there have been many advances with the use of nanotechnology, there have been some limitations as well due to the adverse effects from nanomaterial exposure. There can be toxicity due to the distribution, uptake, and accumulation of the nanoparticles. Quantum dots have been studied for cancer imaging with animal models but are highly toxic due to the cadmium heavy metal properties. There needs to be more research on whether nanoparticles are toxic to non-targeted tissue. Cancer nanotechnology is still in its early stages. It is unknown how well nanoparticles can penetrate targeted tumor tissue. Nanoparticles need to be better modified to be less injurious to healthy tissue and more effective at tumor targeting for the development of better cancer treatment methods and diagnostics.
Nanotechnology is a field that involves creating devices of miniscule size to enhance transport for delivery of drugs and to improve diagnosis and treatment of cancer. Due to its small size and structure, these tiny particles have been found to be effective at penetrating through barriers in the human body to get to cancerous tissue. The tiny particles can also be designed to specifically attach to tumor cells by linking them to a specific tumor cell structure. There has been a new study that has looked at how these miniscule particles can pass through barriers and attach to brain tissue. This is useful because these particles can be loaded with dye and cause a visible color change so that they are able to be seen by neurosurgeons during an operation to remove the tumor. The study analyzed how well these tiny particles are visualized by looking at the properties of how well the color change can be perceived by the human eye. They also explored how well the particles are taken up by the brain tumor cells. This research is important because it can help neurosurgeons during an operation by allowing them to see tumors that are hard to visualize. Brain tumors called gliomas are very aggressive and can spread very quickly. Many brain tumors that are considered inoperable because of its location and because of the difficulties surgeons would face getting to the tumor without destroying normal brain tissue. However, with the use of this technology, these brain tumors may become some day operable. It has been proposed that with the use of these particles, surgeons would be able to visibly distinguish tumor tissue from normal brain tissue.
However, the development of this technology is limited and is only in its early stages, but it is a good start towards advancement. More research needs to be done on the use of this method to help with surgical treatment for brain tumors. First the study was not done in living organisms and it would be important to see how well the particles attach to brain tumor cells in living organisms. Additionally, more research needs to be done on its effects on human tissue. There might be many possible side effects of the dye used and it is unclear what the toxicity levels are for the dye uptake in other tissues in addition to normal brain tissue. It is also unclear whether the dye will be delivered systemically into the circulation and be toxic to other tissues. There needs to be more research done on animal models to ensure safety of using these particles to get through the blood brain barrier. However, this study is a stepping stone to address one of the challenges that neurosurgeons face at identifying tumor cells and visualizing, and distinguishing tumor cells from normal cells during an operation. Since there is not enough research yet in the literature to prove the safety and efficacy of using this method to guide surgery for removal of brain tumors, I would currently not encourage using this approach for a patient. However, this study did reveal that there is great potential for future advances and research for using this approach.
The study was an experimental study that used an in vitro approach to look at how well tagged dye loaded nanoparticles attached to brain tumor cell surface receptors. The study analyzed how well the nanoparticles could be visualized with the dye by looking at the different properties such as saturation, hue and brightness. It also analyzed how well the nanoparticles could be taken up by the tumor cells and compared different cell lines that expressed different levels of the tumor cell surface receptor nucleolin. The nanoparticles were additionally tagged in a time and dose dependent manner so that it can also be determined quantitatively how well the nanoparticles were taken up by the tumor cells. As the study stated, since the experiment was done in vitro, it is hard to determine whether the same results apply to in vivo studies to see if the characteristic of accumulation and visualization of nanoparticles to glioma cells still hold true.
The study did effectively show whether there was an increased affinity of the targeted nanoparticles to glioma cells by comparing it to non-targeted nanoparticles and showed that there was a specific cell-surface receptor interaction between the nanoparticles and the tumor cells. The study looked at how relative nucleolin expression was to the uptake of the nanoparticles and their comparisons to different tumor cell lines with different nucleolin expression showed that there was a correlation between nucleolin expression and saturation. The positive aspects that this investigative study had was that it carefully looked at the affinity and binding characteristics the nanoparticles had to the glioma cells. This is important not only for using this type of method for visualization of tumor cells during a tumor resection, but might be applicable for using this method to improve other imaging modalities. The study could have improved on its methods by additionally investigating more on the properties of the dye and comparison to other dyes that could be used. Additional studies analyzing toxicity levels and other properties of the dyes such as its effect on uptake in other tissues might be effective. As the article mentioned there has not been a lot of data on the effects of dye loaded nanoparticles on tumor models. Additional studies on nanotoxicity of the dye loaded particles in animal models in vivo might be important future investigations. Other studies on how well the nanoparticles cross the blood brain barrier might also be valuable. These studies might be difficult to carry out without first setting up in vivo tumor animal models before doing the investigations.
The study did not seem to have any conflicts of interest. As the study reported, it was funded by grants from the National Institute of Biomedical Imaging and Bioengineering, the National Cancer Institute, and the Congress of Neurological Surgeons Basic/Translational Resident Research Fellowship. It was stated that there were no financial or institutional conflicts of interest. Since the study was done in vitro, there were also no ethical concerns involving the safety and health of patients.