26 August 2016

Aptamers have emerged as an exciting and promising new means of treating neurological disease, with the potential to fundamentally change the way we approach CNS-targeted therapeutics. With the propensity to cross the blood–brain barrier (BBB), Aptamers can target specific cell or signalling systems, respond to endogenous stimuli, or act as vehicles for gene delivery, or as a matrix to promote axon elongation and support cell survival (Cheng et al. 2013).

Functions of the Blood-Brain Barrier

The BBB regulates brain homeostasis and the transport of endogenous and exogenous compounds by controlling their selective and specific uptake, efflux, and metabolism in the brain.Brain capillary endothelial cells, pericytes, astrocytic foot processes, and nerve endings terminating on the capillary surface constitute the BBB (Pardridge et al. 2013).

The unique structure of the BBB hinders many therapies directed at brain pathologies. Several non-invasive strategies have been proposed to overcome this problem. This includes delivery through (Cheng et al. 2013):

  • Nasal mucosa,
  • osmotic opening of the BBB,
  • nanoparticle coating,
  • transporter vectors,
  • Viral vectors

How can Aptamers Cross the Blood-Brain Barrier?

Given the chemical and physical attributes of aptamers, it is unlikely that they enter the brain via paracellular aqueous routes or transcellular lipophilic pathways. However aptamer may enter via adsorptive-mediated transcytosis, channel and/or receptors for uptake or fluid-phase pinocytosis (Hanss et al. 1998). Recent work suggests that a quadruplex-forming DNA aptamer binds to nucleolin via macropinocytosis. Cheng et al (2013) identified an aptamer that can enter brain endothelia cells under physiological conditions, and in vivo, into the brain parenchyma.


Figure 1 Schematic representation of the blood-brain barrier and aptamers toward targeted therapy of neurological diseases (Rakesh, 2016).

Brain Tumour

The most lethal form of malignant tumour in adults is glioblastoma. This type of tumour is characterised by rapid growth and is highly invasive with its capacity to spread into critical neurological areas within the brain. In 2012, Kang et al. developed two aptamers with high affinity and specificity against gliblastoma cells and without any nonspecific binding to normal astraglial cells or normal brain tissue. Kim et al (2013) was also able to develop tumour initiating cells (TIC) aptamers that specifically bind to TICs with excellent affinity. These aptamers select and internalize into Glioblastoma (GBM) cells that self-renew, proliferate, and initiate tumours (Kim et al., 2013).

PEG–PLGA nanoparticles incorporating a DNA aptamer to target nucleolin, a molecule that is highly expressed in the plasma membrane of both cancer cells and tumour endothelium enhanced the anti-proliferative effects of paclitaxel against C6 glioma cells in vitro (Srikanth and Kessler, 2012). These aptamer nanoparticles strikingly reduced C6 glioma xenograft volumes in nude mice, and prolonged survival of animals with C6 intracranial gliomas compared with treatment with either paclitaxel alone or paclitaxel loaded into undecorated nanoparticles. (Srikanth and Kessler, 2012) Importantly, the aptamer-decorated nanoparticles showed greater efficacy than undecorated particles highlighting the value of targeted delivery (Srikanth and Kessler, 2012).

Aptamer Group

Aptamer Group takes a high-throughput approach using liquid handling robotics and dedicated researchers to identify aptamers against novel and significant targets. We are committed to finding the perfect aptamers to your target and use a proprietary selection technique to identify high affinity aptamers with specificity in as short as 3 months.

Aptamer Group’s biomarker discovery, diagnostic and therapeutic divisions aim to conduct further research in the prevention, diagnosis, and treatment of neurodegenerative diseases. Through our know-how and key collaborators, we are able to help facilitate the development of aptamers as therapeutics or diagnostic devices for your target of interest.

White paper :- Our white paper on Aptamers in Neuroscience will be posted on the website soon. For any further information, please contact info@aptamergroup.co.uk


Cheng, C., Chen, Y. H., Lennox, K. A., Behlke, M. A., & Davidson, B. L. (2013). In vivo SELEX for Identification of Brain-penetrating Aptamers. Molecular Therapy. Nucleic Acids, 2(1), e67–. http://doi.org/10.1038/mtna.2012.59

Pardridge WM. Biopharmaceutical drug targeting to the brain. J Drug Target. 2010;18:157–167.

Rakesh, N., Veedu (2015) Aptamers:Tools for Nanotherapy and Molecular Imaging