Nanomedicine: Activity 2
Aptamers and Nanoparticles:
What Are They and Why Are They So Potentially Useful?
Click the word document to the right if you would like to download the activity. Otherwise proceed down the page for the activity.
Introduction
Aptamers are nano-sized three-dimensional structures that can be made up from a peptide chain (small amino acid chain) or out of single strands of nucleic acid chains called, deoxyribose nucleic acid (DNA) or ribonucleic acid (RNA) .
Aptamers that are made from DNA or RNA are super small (nano size) and have low immunogenicity - ability of a substance to set off a defensive immune system reaction in the body . This is because they resemble the same material that is in the nucleus of cells. This makes them very effective and ideal for navigating the body into many tightly crammed cell tissues.
They can go by other names such as ligands which are molecules that bind to a metal ion or chemical antibodies because they are chemically made versions of antibodies. Antibodies are protein molecules made by an organism’s own body and can seek out and attach to specific molecules or receptors in the body. They are produced by the human or animals immune systems as a defence mechanism against foreign germs that try to enter the body .
Aptamers are made from DNA - the genetic material found inside cells.
Image: from wix
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Image shows two molecules in blue housed inside a nanocapsule shown by the grey.
Image by: M stone [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons
Aptamer’s are a relatively new technology, only discovered in the 1990’s. This was a chance observation by scientists who were working with viruses, noticing small segments of RNA that would attach to some proteins strongly . This sparked their own and countless other interests, leading to lots of further research into the use of small single stranded DNA or RNA for a whole range of uses; particularly, in targeted cancer treatment research to see if they could bind to cancer cell receptors , but also DNA’s ability to be folded into 3D shapes. These shapes can form nano-sized capsules which can be an incredibly useful tool when utilised for nanomedicine to treat cancer .
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Cell receptors are specifically shaped structures on cells that are used to receive signals and cause a response in a cell . The receptors have a ‘key’ which connects with the receptor causing a response in the cell.
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This activity will focus specifically on DNA/RNA aptamer and nanoparticle technologies, exploring what they are and how they work with a focus on cancer treatments.
What is are aptamers and nanoparticles?
Before getting into some research, think of any possible benefits to using nano sized molecules such as DNA or RNA in medicine? Write your thoughts down and discuss with your class mates and teacher.
Come back to your thoughts on this later and add any additions or revise your your answer.
Image shows an aptamer with a molecule attatched. The yellow part is the DNA which forms the aptamer - it has folded into the 3D mass shape which the yellow shading highlights. Its the structure it forms that binds with cell receptors.
Image by Fdardel [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], from Wikimedia Commons).
Aptamers
To answer the following questions, click on the link below which is hyperlinked to a scientific journal article page.
A scientific journal article is an article that has been published by a scientist/s about some research they have done that has been peer reviewed by other scientists to check the procedure has been carried out properly and that the information is accurately interpreted from their findings. They are one of the most reputable information sources you can get when doing research.
The article you will be looking at is called, “Aptamers as targeted therapeutics: current potential and challenges”. The link will take you to the Nature reviews webpage, which contains an abstract of the article.
An abstract is a summary of a journal article that gives you the key findings from the paper. On the webpage there is also a summary of key points from the article.
Read this page: https://www.nature.com/articles/nrd.2016.199 and answer the questions below.
Research time. Image from Wix.com.
Part A - Questions
1. What are aptamers made of?
2. Define the following words:
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Immune system
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Antibody
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Immunogenicity
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Receptors
3. What are the beneficial properties of aptamers? List them.
Part B - Sketching Nanomedicince Technologies
Now watch the next clip showing a nanoparticle with the antibodies bound into the membrane. With current technology these antibodies in the membrane could also be aptamers that could bind to the receptor on the cancer cell.
Watch the following clip up until 1minute and 8 seconds: https://www.youtube.com/watch?v=1QwyMWM0Jjg
Draw a sketch of the nanoparticle from the clip, remembering that you are drawing the nanoparticle with aptamers embedded into its surface, not the antibodies they reference in the clip.
Image from Wix.com.
Bringing it all together: building an aptamer-nanoparticle complex.
After watching the clips showing two different versions of nanotechnologies: nanoparticles and aptamers it is now time to try modelling an aptamer bound to a drug or a nanoparticle with aptamers attached using pipe cleaners and plasticine.
Include a design sketch of your nanoparticle/ aptamer bound drug and label it. Explain to the teacher how your sketched example replicates this concept before making it.
Image: Taken by Hayley Wilson
Model your sketch using pipecleaners, plasticine and foam spheres and take a photo of it.
Label the picture for your reference later.
If you unsure of how to model aptamers using pipe cleaners, watch the video demonstration below or ask the teacher.
Image: Modeled example of aptamer nanocapsule complex (at top) and aptamer linked to a chemotherapy drug (at bottom). Image taken by Hayley Wilson.
To the left is an example of a nanoparticle attached to an aptamer and a nanocapsule attached to an aptamer modeled from pipe-cleaners.
The pink and yellow receptors in the image are cell receptors. These cell receptors are not made from DNA.
The aptamer component in these pictures are the red and orange parts of the pipecleaners which are sequences of DNA that have folded to form the '3D Structures'.
The purple plasticine are the chemotherapy drugs - attached to the blue linker at the bottom or contained inside the green nanocapsule at the top.
Aptamer Modeling Video Example
Aptamer Modeling Video: created and filmed by Hayley Wilson on the 6/9/2018.
References
1. Sun, H, & Zu, Y 2015, 'Aptamers and their applications in nanomedicine', Small (Weinheim An Der Bergstrasse, Germany), vol. 11, no. 20, pp. 2352-2364. Available from: 10.1002/smll.201403073. [28 August 2018].
2. Bourghouts, C. Kunz, C & Groner, B., 2005, ‘Peptide aptamers: recent developments for cancer therapy.’, EXPERT OPINION ON BIOLOGICAL THERAPY, 5(6), 783-797
3. Shigdar, S, Luczo, J, Wei, M, Bell, R, Danks, A, Liu, K, & Wei, D 2010, Aptamer Therapeutics: The 21St Century's Magic Bullet Of Nanomedicine, n.p.: Bentham Science Publishers, Deakin Research Online, EBSCOhost, viewed 28 August 2018
4. Immunogenicity. (n.d.) Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. (2003). Retrieved September 5 2018 from https://medical-dictionary.thefreedictionary.com/immunogenicity
5. Chemistry Libretexts, 2018, “Ligands”, https://chem.libretexts.org/Textbook_Maps/Inorganic_Chemistry/Supplemental_Modules_(Inorganic_Chemistry)/Coordination_Chemistry/Properties_of_Coordination_Compounds/Ligands retrieved: 6/9/2018.
6. The Editors of Encyclopedia of Britannica, 2000, “Antibody Biochemistry”, https://www.britannica.com/science/antibody , viewed 6/9/2018.
7. Dollins, C.M., Nair, S. & Sullenger, B.A., 2008, ‘Aptamers in immunotherapy.’ Hum. Gene. Ther, 19, 443–450. [Google Scholar]
8. Henri, J, Macdonald, J, Strom, M, Duan, W, & Shigdar, S 2018, ‘Aptamers As Potential Therapeutic Agents For Ovarian Cancer’, Biochimie: Elsevier, Deakin Research Online, EBSCOhost, viewed 28 August 2018.
9. Ozalp, V, Oktem, H, & Eyidogan, F 2011, 'Aptamer-gated nanoparticles for smart drug delivery', Pharmaceuticals, vol. 4, no. 8, p. 1137-1157. Available from: 10.3390/ph4081137. [28 August 2018]
10. Féger J1, Gil-Falgon S, Lamaze C., 1994, “Cell receptors: definition, mechanisms and regulation of receptor – mediated endocytosis.”, Cell Mol Biol, Vol.40, Iss. 8, pp. 1039-61.
11. Zhou, J, & Rossi, J 2017, 'Aptamers as targeted therapeutics: current potential and challenges', Nature Reviews Drug Discovery, no. 6, p. 440. Available from: 10.1038/nrd.2017.86. [5 September 2018
12. Wilson, H., 2018, "Aptamer Modeling Video" video clip.