NANOTECHNOLOGY ADVANCEMENTS IN CANCER THERAPY
IBRAHIM, Gladys Zugwai
DOKITA Editorial Board Member
Cancer is simply defined as “a disease in which abnormal cells divide without control and can invade nearby or distant tissues”.  It remains one of the most difficult medical conditions to manage and a major cause of mortality for few reasons. Some of these reasons are: the difficulty in targeting cancer stem cells, resistance mechanisms of stem cells to drugs, difficulties with making a diagnosis, and the metastatic ability of cancerous cells making it difficult to target.  Due to this, the notion of cancer being an incurable disease has thrived thereby making it one of the most dreaded medical conditions. If diagnosed early and in a resectable area, prognosis is good and the chance of metastases is low. Other common cancer treatment modalities are chemotherapy and radiotherapy which are useful in managing metastases and shrinking tumour size for easier resection.
Brief History of Nanotechnology
Physicist Richard Feynman is considered the Father of Nanotechnology, being the first known person to describe the concept behind nanoscience and nanotechnology long before the terms were used, in his talk at an American Physical Society meeting at the California Institute of Technology (CalTech) on December 29, 1959 titled “There’s Plenty of Room at the Bottom – an Invitation to Enter a New Field of Physics”. He described the ability of scientists to harness individual atoms and molecules which forms the basis of the practice of nanotechnology.  The exact term ‘nanotechnology’ was coined in 1974 by Norio Taniguichi of Tokyo Science University where he described it as the process of separation, consolidation, and deformation of materials by one atom or one molecule. 
Nanotechnology can be simply defined as the “imaging, modelling, measuring, design, characterization, production, and application of structures, devices, and systems by controlled manipulation of size and shape at the nanometer scale (atomic, molecular, and macromolecular scale) that produces structures, devices, and systems with at least one novel/superior characteristic or property”. It deals with the “understanding and control of matter at dimensions between approximately 1 and 100 nm”.  For context, a strand of human hair and a sheet of newspaper are about 100,000nm thick so nanotechnology deals with matter as tiny as a strand of human hair or a sheet of newspaper divided into 1,000 to 100,000 places.
Different ways of manipulating matter at nanoscale exist but the two commonest methods are the “top-down” and “bottom-up” methods, where a nanomaterial is either made by removing the unwanted parts of a block of material till the wanted shape and size is attained or the use of self-assembly which is nature’s self-organizing process to build something up.
The major downside of the longstanding strategy of cancer therapy which is basically flooding the bloodstream with substances that are toxic to the tumour cells is that these cells are not dissimilar enough from the normal cells, and so the healthy cells are also destroyed in the process. This is made obvious by the commonly known side effects of chemotherapy which include hair loss, weight loss and other serious disorders. Even though effective, a combination of these drugs administered over a long period have detrimental effects on the overall health of the patient. Nanotechnology-based management, however, provides the advantage of targeting treatment to the tumour cells with lesser effect on healthy cells.
Nanotechnology has proved itself useful in both the diagnosis and treatment of cancer. It is believed that the processes that cause cancer happen at a nanoscale of about 1 to 100nm, and so, the goal of nanotechnology in cancer therapy is to manage cancer at this extremely tiny level.
Basis of Nanotechnology Based Cancer Therapy
Angiogenesis – the formation of new blood vessels – is one of the hallmarks of cancer tumours which gives it the ability to grow rapidly. Tumours produce disordered blood vessel networks that are fundamentally different from normal vasculature due to aggressive expansion of the neoplastic cell population and accompanying upregulation of pro-angiogenic factors. Tumuor vasculature is characterized by abnormal structural dynamics and immature, convoluted, and hyperpermeable vessels. The complicated tumour vasculature is often a disordered network of vessels with no obvious distinction between arterioles, capillaries, and venules.  The dysregulation in these vessels causes what is known as the “enhanced permeability and retention (EPR)” effect and this forms the basis of the application of “passive targeting” – one of the modalities of nanotechnology in cancer management. Reduced lymphatic drainage, larger fenestrations, and gaps between endothelial cells, ranging from 200 to 1200 nm, compared to normal endothelium with pores ranging from 10 to 50 nm, all contribute to the EPR effect.
“Active targeting” on the other hand involves the binding of nanoparticles through ligands to specific targets on tumour cells. Selective delivery is achieved by the recognition of the targets by nanoparticles , receptor-mediated endocytosis enabling uptake, and subsequent release of the payload into the nucleus or cytoplasm.  Receptor ligands could be any specific peptides, antibodies or any other structures that are uniquely expressed by the tumour. An example is the overexpressed αvβ3 integrin on a number of tumour cells and largely absent in healthy tissue.
Drug Delivery Systems
Polymeric nanoparticles are the most investigated drug delivery system for cancer therapy , which are organic-based nanoparticles that are either nanocapsular or nanospherical in shape. In the former, the active ingredient and the polymer are evenly dispersed, and in the latter, the active ingredient is surrounded by a polymer shell. Benefits of polymer nanoparticles include sustained release, protection of drug molecules, the ability to combine treatment and imaging, and specific targeting. They are used for drug delivery and diagnostics. Drug delivery with polymer nanoparticles is highly biodegradable and biocompatible.  Polymers can be isolated in a “top-down” fashion from their natural sources for example, chitosan produced from chitin or synthesized in a “bottom-up” fashion to the desired structure as in poly-lactic-co-glycolic acid (PLGA). Abraxane which is paclitaxel bound to albumin is the first Food and Drug Administration (FDA)-approved polymer formulation for treatment of metastatic breast cancer and lung cancer. 
Liposomes are another well-explored method of delivering drugs. The major problem associated with these lipid-based vehicles include rapid uptake by the reticuloendothelial system (RES), hence rapid clearance from the body. However, more recent preparations of this compound involve coating of it with polyethylene glycol (PEG) – a hydrophilic substance, to overcome this challenge.  The first ever approved nanoparticle-based treatment of cancer (in 1995) falls under this category. Doxil which contains a chemotherapeutic agent named doxorubicin and delivered via PEGylated liposal carriers is useful in the treatment of Kaposi’s sarcoma.  
Other methods of drug delivery systems include polymeric micelles, dendrimers, nanoshells (usually composed of a silica core surrounded by gold), and quantum dots.
More Recent Developments
Worthy of note is the most recent development in nanoscience for cancer therapy: Laser-Activated Nanotherapy (LANT) multicancer treatment, which is currently in trials and is popularized by Multidisciplinary Physicist Dr. Hadiyah-Nicole Green. In her words, the LANT system “enables the combination of tumour receptor site targeting, targeted nanoparticle delivery, fluorescent imaging and laser-activated nanoparticle therapy that results in marked tumor regression in mice”.  Dr. Green founded the Ora Lee Smith Cancer Research Foundation, named after her late Aunt who died from cancer after expressing that she would rather die than experience the detrimental side effects of chemotherapy and radiotherapy. This fueled her passion to research into treatment modalities with lesser side effects.  In the LANT system, when viewed with imaging equipment, FDA-approved nanoparticles enable tumour cells to glow. The nanoparticles are then activated and heated by a laser, causing the cancer cells to die from heat. When used separately, the laser and nanoparticles are both safe, enhancing the treatment’s capacity to target cancer cells while avoiding healthy cells. A board certified pathologist validated the disappearance of a mouse tumour after 15 days of therapy during a trial. 
Available from: https://oralee.org/research/
Nanotechnology offers the possibility of improvement in the management of cancer and without the added side effects of treatment. Further studies are required in identifying unique properties of different cancer types to provide information on the type of nanotechnology tools that can be used to target them. This evolving field also offers medical students and new health practitioners that are interested in research with a large pool of questions to solve. Another up-and-coming area of interest in nanotechnology-based medicine is immunotherapy which leverages on a patient’s own immune system to fight cancer by the delivery of immunostimulatory and immunomodulatory molecules. In light of all recent advancements, the future of cancer therapy surely looks bright.
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