Habiba Abbasi
Nanotechnology is a new and growing area of science and engineering concerned with the use of small scale materials. A fascinating application of such tools have been in the diagnosis and treatment of brain tumours. As such, Qiaojing and colleagues have published a paper examining the use of nanotechnological tools in the prognosis of brain tumours. Although there are obstacles yet to be overcome in the use of nanomaterials to diagnose and treat brain tumours such as neurotoxicity, the future of this treatment looks promising.
Qiaojing and colleagues’ paper reviews the recent developments of nanoparticle-based diagnostic tools and drug delivery systems. In particular, it examines unique properties of different nanoparticles, application to animal models, clinical trials and limitations in the use of nanotechnology.
Glioblastoma multiforme (GBM) is the most aggressive and lethal form of brain tumour and conventional treatments still have undesirable survival rates. Moreover, there are limitations of surgical removal due to its infiltrative growth, making it very challenging to treat. Chemotherapy using temozolomide with radiotherapy is currently used to treat GBM, but there are several limitations including neurological toxicity. Diagnosis of GBM is currently conducted using medical imaging such as magnetic resonance imaging, computerised tomography and positron emission tomography. However, these tools are not sensitive enough to detect smaller GBM tumours and cannot differentiate between different cell types.
Nanotechnological tools can be used in the diagnosis and drug treatment of brain tumours such as GBM. An advantage of using such materials includes their multifunctionality as an anticancer drug, an imaging agent and a tumour specific ligand.
Outlined below are some of the nanoparticles examined in this study including their function, applications and disadvantages.
| Function | Applications | Disadvantages |
Gold-Based | Accumulate at tumour site and promote apoptosis of cancer cells by releasing heat to damage the cellular structure of cancer cells. They also prevent the growth of new blood vessels. | Methotrexate conjugated with gold nanoparticles shows an increase in cytotoxicity and tumour uptake compared to free methotrexate. | Due to physical dimensions, catalytic properties may be promoted, increasing toxic reactivity with the environment. |
Silver-Based | Hinder DNA duplication and promote cancer cell apoptosis. They also prevent the growth of new blood vessels. | A 5-fold survival rate was discovered in the C6 glioma-bearing mice after administration of citrate-capped silver nanoparticles with concurrent 10 Gy-radiotherapy. | Can be toxic due to size, exposure and interaction with microenvironment. |
Magnetic
| Used as both a drug delivery system and in diagnostic imaging. | Silica-coated magnetic iron oxide nanoparticles are used for diagnostic imaging of GBM tumours due to their high accuracy. | There is risk of generating reactive oxygen species which can result in normal cell apoptosis.
High levels of bare Fe2O3 nanoparticles may cause DNA damage/mutations, unwanted inflammatory responses and disruption to cellular cytoskeletal arrangements. |
Lipid-Based (liposomes, solid lipid nanoparticles, nanostructured lipid carriers) | Use in tumour imaging and delivery of anti-cancer drugs to the brain. | Liposomes loaded with quantum dots present higher permeability and retention rate in the brain as compared to free quantum dots, aiding in tumour imaging applications | Due to the structure of these nanoparticles there is risk of expulsion of the encapsulated drug. |
Dendrimers | Has capacity for slow drug release, low toxicity and increased tumour uptake. | PEGylated PAMAM dendrimers conjugated with tumour targeting folic acid can be used to improve the permeability of anti-cancer drugs across the BBB compared to free anti-cancer drugs. | The surface of dendrimers are toxic, but can be coated with polyethylene glycol (PEG) to reduce toxicity. |
Polymeric Nanocarriers | Use as a drug delivery system. | Epirubicin, a potent anti-glioblastoma drug conjugated to polymeric nanocarriers effectively suppresses the growth of GBM. | Long-term effects of polymers including neurotoxicity have yet to be confirmed. |
In the diagnosis and treatment of GBM, nanoparticles are mostly delivered intravenously, which target cancerous cells passively or actively. Passive targeting involves the diffusion of nanoparticles across the tumour blood vessels and accumulate within the tumour tissues and active targeting involves the selective binding of drug molecules to receptors on tumour cells using nanoparticles.
The blood brain barrier (BBB) is a barrier between blood vessels and the brain. It functions to protect against pathogens and toxins accessing the brain whilst allowing nutrients to enter. There are transport pathways that can be exploited to allow the transport of nanoparticles across the BBB such as carrier-mediated transcytosis, adsorptive-mediated transport and receptor-mediated transcytosis.
The blood brain tumour barrier (BBTB) is a barrier between blood vessels and tumour cells that delivers nutrients to tumours. As the tumour progresses in GBM, the BBTB will increase in permeability allowing larger molecules to enter the brain. This can be exploited to enable nanoparticles to reach tumour tissues using active and passive targeting.
Applications of nanoparticles in the treatment of GBM are promising. As such, the European Medicines Agency has approved the use of a nanotechnological system called “NanoTherm®” as a treatment of GBM in 2013. NanoTherm® uses aminosilane-coated SPIONS (magnetic nanoparticle) to ablate tumour cells when exposed to alternating magnetic fields. This is a non-invasive treatment and is able to target tumour cells in the brain and other sites of the body.
Considering the limitations of nanotechnology in the diagnosis and treatment of brain tumours, there have been great advancements in the use of nanotechnological tools in the treatment of novel tumours such as GBM, improving the quality of individual’s lives.
References
Chen, Q., Lin, KTQ., Li-Wen, NSY., Hui, SHC., and Ping, ACM. (2022). Nanotechnology: A Better Diagnosis and Treatment Strategy for Brain Tumour? Journal of Young Investigators, 25(3), 33-47, available: 10.22186/25.3.1.2
Corrections: May 3, 2022
Corrected ambiguity in the provided definitions of Blood Brain Barrier and Blood Brain Tumour Barrier within the article.