Nanomedicine in Cancer
Cancer remains one of the most difficult illnesses to treat and is a momentous cause of morbidity and mortality. With over ten million incidences being detected every year globally, cancer is the second most prominent cause of morbidity in the globe. What makes the disease more difficult to treat is the existence of multiple phenotypes of cancer in any given tumor that upsurge the ability of the cancer cells to evade monotherapy. Without the eradication of all cancer cells during therapy, the remaining cells evolve, grow, and reconstitute the tumor (Taratula, et al., 2011). Also, classical cures for cancer such as radiotherapy, chemotherapy, and surgery exhibit numerous adverse side effects that have led to the search for novel ways of mitigating the menace. Nanotechnology platforms that include liposomes, polymers, and Au/Si/polymer shells can, however, be utilized in addressing the heterogeneity and adaptation of cancer. They have been established as having chemical and physical properties that can be used in the diagnosis, monitoring, and treatment of cancer (Sumer & Gad, 2008). This ability to be utilized in simultaneously diagnosing, monitoring, and targeting cancer cells is what makes them critical for fighting cancer.
As nanotechnology use grows, there is an inadequacy of research and information on how to best utilize it and hence there is a need to delineate how it works to get a feel of what is required in the future. Moreover, due to the its relatively new emergence, the ethics, legality, and implications of the technology has not been well researched and addressed.
This review of literature will research the outcomes of prior studies and nanomedical theory in order to gain a better understanding of nanomedicine, its potential drawbacks and future potential. It will also aim to delineate the implications, both social and environmental, of using the technology in cancer therapy, and delineate how these potential adverse implications can be mitigated.
Does nanomedicine present an advantage over traditional methods of cancer therapy?
- What are the potential uses of nanotechnology in cancer therapy?
- What are the future directions of this form of technology in cancer diagnosis, monitoring, and treatment?
- What are the potential hazards and limitations of using nanomedicine in cancer?
- Does this form of technology have social and environmental impacts? If so, how can these be mitigated?
How it works
The new nanomedicine incorporates multiple functionalities such as cell targeting and ultrasensitive imaging and therapy into the system in a way that traditional molecular-based therapies cannot. It is particularly fundamental in the timely uncovering, monitoring, and cure of cancer. Diagnostic imaging is first utilized in characterizing every cellular phenotype present in the tumor (Sumer & Gad, 2008). Full body imaging is utilized in this process, since, without full molecular characterization, the full breadth of the phenotypes present within a tumor and the tumor cells that have metastasized to other locations will not be achieved. The nanomedicine technology is then used to target multiple tumor markers simultaneously, thereby ensuring that the heterogeneity and adaptation difficulty is countered. Repeated molecular analysis and targeting is done to address any additional adaptation as well as modify the targeting strategy. Developing a platform with the said capabilities is proving a herculean task, but some advances have been made (Sumer & Gad, 2008).
These nanomedicines are delivered to the tumor cells through two mechanisms; passive and active. The passive mechanism entails accumulating the nanomedicines within the tumors through an enhanced retention and permeability effect. The active targeting encompasses adding ligands to the nanomedicines to augment drug uptake in cancer cells. The most frequently utilized ligands are antibodies due to their high specificity and affinity as well as them comprising huge NH2 and COOH groups. Also, most antibodies are already included in the approved list of cancer treatment drugs (Gao, Feng, & Guo, 2010).
Various classes of nanostructures such as quantum dots, magnetic, polymeric, and metallic nanoparticles have been used in diverse ways in the treatment of cancer. Quantum dots are utilized in labeling and detection while magnetic ones are utilized in sorting cells, delivering drugs, and hyperthermia therapy (Gao, Feng, & Guo, 2010). Polymeric nanoparticles are utilized in encapsulating molecules that increase the safety and efficiency of delivering drugs owing to their high solubility that allows enhanced permeability and retention of the drugs in the tumor. Of all the nanoparticles currently in play, metallic ones have proven quite useful and flexible in cancer imaging due to their size, shape, and tenability of their properties.
Colloidal gold nanospheres, in particular, have numerous uses in cancer imaging. They are easy to prepare, their size can be varied, and their citrate capping is easy to replace and use with various ligands including antibodies. These noble metal nanorods are relatively bio-safe, and their surface enables multi-functionalization (Huang, Jain, El-Sayed, & El-Sayed, 2007). Their distinctive optical properties make them well suited for the moderately novel photo diagnosis and phototherapy.
The unique optical properties of gold nanoparticles include the ability to absorb, scatter, re-emit, and enhance any spectroscopic molecular signals better than other particles. When the size of the nanorods is increased, there is an upsurge in the scattering-to-extinction ratio, and this makes gold nanoparticles best suited for either optical imaging or photothermal treatment. Recent studies show that when antibody conjugated gold nanoparticles target cancer cells and tissues, the SPR scattering of these particles under monochromatic light makes it easier to visualize them and allow for an effective labeling of the cancer biomarkers (Huang, Jain, El-Sayed, & El-Sayed, 2007).
Besides imaging, the gold nanoparticles can be utilized in selective laser psychanalysis owing to their efficiency and intensity of photothermal absorption and conversion. Their tenability is also a great asset owing to its several applications in imaging and psychoanalysis. As evinced herein, gold nanoparticles have diverse uses in cancer screening and therapy, and with more research and development, they are bound to impact on the future of nanotherapy greatly.
Overview of directions in the development of nanomedicine platforms
New Cancer-specific targets have been characterized that provide larger therapeutic indices. They encompass cancer-specific enzymes, angiogenetic expressions, and repair and replication alterations. Novel therapeutic agents and targeting ligands with a high binding infinity have also been discovered, but these have a tendency to enable cancer cells bypass targeted cells and develop higher resistance than they did with the older chemotherapy agents. The resistance can, however, be reduced by combining monoclonal antibodies and multiple receptors. It has been shown that a single nanomedicine formulation can achieve the synergetic effect articulated above in a way that mitigates the intricacy of multiple drug combinations (Sumer & Gad, 2008). With further engineering, the Nano platform will achieve this synergetic effect as well as reduce the systemic toxicity of the new chemotherapeutic agents.
Developments such as nuclear imaging systems provide high-resolution images with superior soft-tissue contrast and anatomical resolution and can be utilized in cancer imaging. This imaging is useful in the systemic tracking of nanoparticles, the pre-validation of appropriate targeting, the mapping of alternative targets, and the provision of real-time data on tumor response to treatment.
Recent progress such as the perfluorocarbon-based system (~200nm) is ideal for use in nanomedicine due to their small size, efficiency in targeting tumor tissues, and ability to provide responsive release mechanisms. The ~200nm, for example, can deliver drug molecules while at the same time being used in ultrasound and MRI detection. The capabilities of these multifunctional platforms are constantly on the rise, but the necessity of a controlled release of the encapsulated agents in tumors adds to the difficulty of developing these nanocomposite materials (Sumer & Gad, 2008).
Biologists in conjunction with technologists have created Nanodevices called Nanobots that have features of auto replication and total autonomy. These Nanobots have the ability to multiply progressively, and thus can be used with fewer hindrances in the treatment of cancer. An example of these nanobots is the EU made vehicle anti-cancer that can transport anti-cancer drugs towards tumor sites and upon locating the target, releases the drugs to selectively destroy the tumor cells without impacting on the normal cells (Gonzalez, 2009).
Hazards and Limitations
Hazards of Nanomedicine in Cancer
Due to the unique reactivity of Nanoparticles, it is highly anticipated that these nanoparticles will impact on toxicity although the impact may differ depending on the type of the nanoparticle utilized. These particles have differing psycho-chemical characteristics, and consequently exhibit different distributions as well as various side effects (Gonzalez, 2009). The interaction of the nanoparticles inside the cells and tissues as well as their toxicity is thus dependent upon the particle composition.
The body distribution profile of Magnetic iron oxide elements, in particular, are reliant on the shape, size, and thickness of the coating, but degradation was revealed to be dependent upon the coating rather than the size of the nanoparticles. Even though these magnetic iron oxide nanoparticles have resulted in zero morbidity, they still present a safety issue in clinical practice. Scientists conclude that it is unclear whether the anaphylactic reactions that occur during therapy using these nanoparticles is as a result of the direct influences of the iron or due to the immunologically mediated mechanism. The same scientists conclude that the toxicity reaction hypothesized is also limited (Gonzalez, 2009).
The main reason for the toxicity hypothesis is that the nanoparticle size creates a potential for them crossing the blood-brain barrier and delivering the drugs into the brain. The small size also allows for the particles to access various cells and cellular compartments such as the nucleus, and this is expected to have significant side effects on the human body.
Nanotechnologies have diverse applications in cancer research and treatment but are very complex and expensive. They are hence available to a limited number of prospective patients and medical facilities. The concept of utilizing nano-assisted imaging thus presents numerous technical challenges before being deemed a portable solution for cancer diagnosis, monitoring, and treatment. Besides the cost demands, the technology also puts too much demand on energy. These systems are also large and portable and thus present many practical difficulties (Gonzalez, 2009). The technique of nanoparticle magnetization using static magnetic fields, for example, requires the utilization of a magnetic field intensity that requires too much energy. Many institutions can not only afford to purchase these machines, but the operational costs are also a major hindrance.
Antibody nanomedicines utilize conjugation procedures that are primarily covalent reactions and even though these covalent reactions are useful in fixing antibodies to nanomedicines irreversibly, and they also impact on the biological activity of antibodies adversely. There are also difficulties in correctly fixing the antibodies to the nanomedicines, and this results in an impaired biological activity of the antibodies (Gao, Feng, & Guo, 2010). Secondly, there are barriers to the binding sites and these impede on how the nanomedicines penetrate into the tumor masses. This results in low outcomes and sometimes zero advantages of using the nanomedicines over the non-targeted medicines. Lastly, targeted nanomedicines still show an affinity for binding to normal tissues, and this leads to some level of toxicity and adverse side effects.
In the area of antibody-nanomedicines, novel strategies that are efficient, discretionary, and moderate should be developed to improve the fixation of antibodies to nanomedicines. Additionally, to achieve rapid and complete penetration of the antibodies into the tumor, nanomedicines that have optimal size, affinity, and a high binding valency should be developed (Gao, Feng, & Guo, 2010). Lastly, antibodies that target specific tumor antigens is also critical.
The utilization of nanotechnology in the detection, monitoring, and treatment of cancer, as well as the creation of safer modalities with few or no side effects, will lead to cancer becoming a more manageable chronic ailment. The nanotechnology also allows a better comprehension of the illness, and shortly, cancer may be eradicated fully (Hui, 2005). Despite these projected benefits, there are various societal and ethical issues to be addressed.
Mamo et al. (2010) highlighted the value of nanomedicine as a breakthrough treatment for diseases that have not been curable, such as cancer. However, the controversy surrounding the advancements in nanomedicine still span from arguments as to the manufacture and use of nanotechnology to the toxicological and pharmacological properties of nanomaterials (Mamo, et al., 2010). Hybrid formed from tissue engineering raise ethical concerns, as nanomaterials are being placed in the human body. Privacy issues have arisen regarding evolving medical information systems that use lab-on-chip diagnostic systems.
Ethical debates regarding nanomedications are more complicated than in other biotechnology fields; however, the Beauchamp & Childress (2008) ethical tenets of beneficence, justice, autonomy, and non-maleficence are the same for all medical fields (Beauchamp & Childress, 2008). The integration of these tenets from the Research & Development process to the implementation of nanomedicine techniques will serve as a guide and as a boundary that fundamentally represent the best interests of society.
Besides the ethical tag, the use of nanomedicine in eliminating cancer will lead to an upsurge in the lifespan of humans, and hence future generations will consist of a large pool of elderly people. This aging society will require more care and attention, and in so doing counterbalance the savings made from efficient cancer nanomedicine.
There are numerous concerns about how the excretion and disposal of nanoparticles will impact on the environment. It is yet unknown how to best process and dispose of these nanoparticles, but it is known that they will constitute a novel class of non-biodegradable pollutants that may adversely impact on human health. Due to their minute size, they can remain airborne for extended time periods and be inhaled by living things. They may also pollute the soil and water, and eliminating them from the environment will be extremely difficult (Hui, 2005).
Addressing the nanotechnology issue
Numerous studies on the repercussions and best practices of utilizing nanotechnology are thus required. Besides studying how nanoparticles interact with the body, there should also be studies on how they interact with the environment. The ethical, legal, and social implications assessment requires the involvement of not only the top brass in government but also the common public who need to be aware of matters concerning them. Nanotechnology education may also prove pivotal inincreasing awareness and understanding.
Cancer is the second leading cause of morbidity in the world, but recent advances in nanotechnology present a way of eliminating the menace. These nanotechnologies present an advantage over traditional cancer cures due to their ability to be utilized simultaneously in diagnosis, monitoring, and treatment. These nanomedicines include polymeric, magnetic, carbon-based, quantum dots, and metallic particles, but metallic particles have been shown to be the most efficient in cancer diagnosis and treatment due to their unique optical properties. Nanotechnology research has picked up speed in recent years, and novel modalities such as the perfluorocarbon-based system have shown great promise. Despite these advances, nanotechnology use is marred with many ethical, legal, and societal concerns. There are concerns about the side effects of nanomedicine use on humans and the environment. In the future, therefore, more attention needs to be focused on addressing these concerns even as the globe gears towards the goal of complete cancer elimination.
Beauchamp, T. L., & Childress, J. F. (2008). Principles of Biomedical Ethics. Oxford: Oxford University Press.
Gao, J., Feng, S.-S., & Guo, Y. (2010). Antibody engineering promotes nanomedicine for cancer treatment. nanomedicine, 5(8), 1141-1145. Retrieved from http://files.nanomedicina.webnode.pt/200000069-a9009a9fa3/Cancro%20e%20nanomedicina%201%20(ingl%C3%AAs).pdf
Gonzalez, C. A. (2009). Nanomedicine in Cancer. In C. Alexandre, Biomedical Engineering (pp. 387-399). Rijeka: InTech. Retrieved from http://www.intechopen.com/books/biomedicalengineering/nanomedicine-in-cancer
Huang, X., Jain, P. K., El-Sayed, I. H., & El-Sayed, M. A. (2007). Gold nanoparticles: interesting optical properties and recent applications in cancer diagnostics and therapy. nanomedicine, 2(5), 681-693. doi:10.2217/174358188.8.131.521
Hui, N. C. (2005). Nanomedicine and cancer. Retrieved from http://www.tahan.com/charlie/nanosociety/course201/nanos/NH.pdf
Mamo, T., Moseman, E. A., Kolishetti, N., Salvador-Morales, C., Shi, J., Kuritzkes, D. R., . . . Farokhzad, O. C. (2010). Emerging nanotechnology approaches for HIV/AIDS treatment and prevention. Nanomedicine, 5(2), 269-285. doi:10.2217/nnm.10.1
Sumer, B., & Gad, J. (2008). Theranostic nanomedicine for cancer. nanomedicine, 3(2), 137-140. Retrieved from