NANOTECHNOLOGY ADVANCEMENTS IN CANCER THERAPY

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”. [4] 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.

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. [5] 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. [6] 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.