Nanoparticles as an alternative to conventional cancer treatment

Luiza Elias Coutinho and Malaika Naeem Sandhu

Authors

Luiza Elias Coutinho is a rising senior at Colégio Militar de Belo Horizonte. Since 2015, she works as a lab assistant at the Universidade Federal de Minas Gerais, doing research in biology fields. She hopes to become a biomedical engineer.
Malaika Naeem Sandhu is a rising senior at Roots IVY, Pakistan. She aspires to be a neurosurgeon in the future and to pursue her passion in Fashion Designing as a side job. She hopes to go to a prestigious university abroad for her undergrad and has various non-academic interests ranging from working out to community service.

Introduction
Today, cancer is one of the most fatal diseases, associated with impending death. It is extremely necessary to find a cure for it as that will not only neutralize the negative effects on humans, but will also ensure that more resources are available for human development rather than draining the resources on surviving.

Cancer is a series of diseases resulting from uncontrollable cell growth and its spreading  into other healthy parts of the body. Today, there are different known types of cancer with variable stages, but the non-regulated development of cancerous cells can ultimately lead to death. Some cancer cells become malignant tumors, capable of metastasizing which means they can spread to other healthy parts of the body, while some cancers do not become malignant tumors(8). Due to cancer’s different patterns and consequences, many kinds of treatments are currently used depending on the cancer type and its severity. Some current procedures used to treat cancer are surgeries, chemotherapy, radiation therapy, photodynamic therapy, immunotherapy, hormone therapy, and stem cell transplant, each with their respective advantages and drawbacks (14).

Surgery can only be used for patients with localized tumors, as it treats cancers that were not transmitted to other areas of the body, whereas chemotherapy and radiation therapy can provoke unwanted side effects such as hair loss, weakness, organ dysfunction, and provoking extreme unintended damage to off target cells(31). In photodynamic therapy, the patient can become sensitive to daylight exposure in the skin and eyes. Hormone therapy can interfere with  the body’s natural ability to produce hormones while stem cell transplants can cause bleeding and increased risk of infection. In the case of an allogeneic transplant, in which healthy stem cells from another person transplanted in your body that make new, healthy blood cells, graft-versus-host disease can develop and cause damage to skin, liver, intestines, and many other organs as the immune cells of the transplanted tissue regard the recipient’s body as foreign and attack the body(22).

The use of nanoparticles

Due to the damage to the healthy cells and side effects on the human body caused by the traditional treatments, nanoparticles are emerging as an alternative of cancer treatment. Nanoparticles are very small objects, between 1 and 100 nanometers in size(27), that can be made of natural and artificial polymers, dendrimers, lipids, metals, and other chemical compounds (26). They are used in a large number of consumer products such as paints, sports materials, sunscreens, and industrial materials. Recently, nanoparticles have emerged as significant players in medicine and genetic engineering, used as vehicles for targeted delivery of growth factors, drugs, genes and oligonucleotides in vivo. For instance, they have brought advancements in the use of tissue engineering, cell imaging, and Magnetic Resonance Imaging (MRI) – a radiology test to form pictures of the body’s internal physiology (28).

But how can nanoparticles act to improve the effectiveness of cancer treatments? What are the differences between conventional treatments and the use of nanoparticles? The use of nanoparticles is rapidly advancing as it solves several problems caused by the already existing cancer treatments like biodistribution, targeting, lack of water solubility, poor oral bioavailability, and low therapeutic indices. They offer several advantages over the commonly used treatments such as the ability to target specific locations in the body, need for less dosages of drugs, and reduction of side effects, since little or no drugs concentrate in non-target areas and the healthy tissues are not damaged(27). Moreover, managed and controlled release of drugs at target sites over a period of days or even weeks has been made possible due to nanoparticles (10, 30).

The main areas in which nanoparticles were used in cancer treatment are molecular imaging and therapy. Molecular imaging is an investigative method that quantifies changes in living organisms, making images and measuring the manifestation of evidential molecular indicators in the various phases of the disease(28). Injection and absorption of nanoparticles into cancerous cells in the body make cancer cells appear different than regular cells in time-lapse microscopy. Meanwhile, various types of therapies use drugs, remedies, and even radiation to treat cancer, but cannot be delivered to the tumors without no damaging the normal cells of the body. In this sense, the application of the modern targeted nanoparticles may be more efficient in the treatment of tumors, as they are able to distribute drugs to cancer cells, with no deviations to healthy cells (14, 11, 25).

Targeted Drug Delivery
         The most important step in improving treatments is better targeting of the remedies to the tumor tissues. The drug can be enclosed in the nanoparticle or attached to the surface(23). Examples of developed drug delivery systems are poly(lactic-co-glycolic acid) (PLGA)(29), liposomes, dendrimers, micelles, and silica nanoparticles. Nanoparticles are used as carriers in cancer diagnosis and therapy as they can accumulate in tumors after intravenous administration. In this way, to ensure that the application of nanoparticles in the treatment of cancer is effective, it is necessary that they are able to reach specific tumor tissues by penetrating body barriers with minimal effect on  bloodstream activity(29). Then, the drugs must attack only selected cancer cells, without reaching normal cells. Following these steps, there is a decrease in treatment toxicity and improvement in the patient’s life (15).

One of the methods for specific delivery of drugs to cancer cells is ligand-mediated targeting(23). In this process, drugs are associated to molecules that bind to specific proteins that are differentially  expressed on target cells and normal tissues. This enhances the selective delivery of drugs to inhibit the growth and spread of tumors. Tumor cells have molecular markers that can be used as receptors to concentrate drugs and nanoparticles at the tumors, making the drugs more effective and reducing side effects. Nanoparticles that reach their target and then release the drugs increases the bioavailability of the drug (12).

Liposomes
Another way of delivering drugs using nanoparticles is loading the drugs into liposomes which is very advantageous as it releases the drugs at selected target and can fight drug resistance(22). The liposomes were the first nanoparticles used in chemotherapy. They are composed of phospholipid molecules surrounding a water particle with sizes varying between 30 nm and a few microns (18). Liposomes are described as efficient agents to improve the delivery of doxorubicin, an antitumor medication, and pharmacokinetics in general. Until recently, there were indications that doxorubicin could also cause cardiotoxicity in some cases, but new technologies are reducing liposomes’ side effects. Some studies show that the antitumor activity increased due to the direct action of doxorubicin in the cancerous tumours. Besides, liposomal doxorubicin was proved to be safe and authorized to be used in cancer treatment. For instance, a doxorubicin HCl liposome injection was able to escape one barrier to nanoparticle circulation, a part of the immune system called reticulo-endothelial system (RES)(32).

Magnetic Nanoparticles
The use of magnetic nanoparticles is also a promising alternative to cancer treatment. Magnetic nanoparticles are particles that can be operated using magnetic fields(13). They are usually made of a magnetic component, like iron, and a functional chemical component. Anti-tumor drugs can be adsorbed on the surface of magnetic nanoparticles, which is then concentrated at the target using an external magnet, releasing the drug where it is needed(16,17). In magnetic fluid hyperthermia, nanoparticles are delivered to the tumor and manipulated using a high frequency magnetic field which can kill the tumor cells as they produce heat that raises the temperature of tumor to 40-46 °C (20).

Gold Nanoparticles

Another method to cancer treatment is the use of gold nanoparticles, which are under study in the fields of drug delivery and photothermal therapy(26). In photodynamic therapy, gold nanoparticles are able to eradicate tumors through producing heat when excited by light at specific wavelengths. Gold nanomaterials have been extensively explored and majority of the agents used nowadays in photothermal therapy are inorganic and non-biodegradable, however, the use of organic nanoparticles to deliver drugs attracted significant attention recently as they are biodegradable (7, 24).

Conclusion

In this way, using targeted nanoparticles to deliver chemotherapeutic agents in cancer therapy offers many advantages to enhance drug delivery and to counter many problems related to conventional chemotherapy. As the nanoparticles enable more tumor visibility, they have a promissory role in imaging. Their role in cancer therapy should also be expanded, along with new strategies for targeting drugs to tumors. There is still much to be improved in targeting drugs to tumors and biocompatibility, but the benefits of nanoparticles can promote their expansion in the scientific field(32). Further investigation of the applications of  drug delivery through nanoparticles will lead to improvements in current methods of combating cancer (3, 19).

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