DNA Cage Matches...possible drug delivery systems?

In the online 1 September 2013 online edition of Nature Chemistry, Edwardson et al. reports the use of dendritic alkyl-DNA complexes attached to DNA 'cubes' as a possible delivery system.  The link to the actual journal article can be found below (unfortunately this journal does not allow for the educational use of its figures without a subscription....)  Please note that you can see figures of the DNA cages on the journal article's webpage.



Site-specific positioning of dendritic alkyl chains on DNA cages enables their geometry-dependent self-assembly

The amphiphilic nature of these cages allow for the encapsulation of small particles...another example of nanotechnology.  Then, through DNA recognition, the encapsulated "contents" of the DNA cages can be released.  This would possibly allow for the site-directed delivery of the contents (i.e. possibly site-directed drug delivery).  What would the possible drawbacks be?  What intrinsic hurdles must be faced in order for this to be successful?  Yes, DNA is more stable (relatively speaking) than its less rigid nucleic acid relative, RNA; however, it is still can be prone to acid-, base-, and metal-catalyzed hydrolysis.  If this method does yield site-directed delivery, then it opens up a plethora of pharmaceutical possibilities.

For a more reader friendly news article about this find, please see the Medical News Today article linked below:

DNA 'cages' may aid drug delivery

Comments

  1. Drug delivery is one of the most important aspects of pharmacology. Researchers have created an ingenious drug delivery method using DNA “cubes”. DNA “cubes” are nanometer sized cubes that are capable of containing small “cargos”. These cargos could be some kind of drug that would be released when specific nucleic acid sequences are present. Researchers are learning through various techniques that many diseases are caused through the overexpression of certain genes in specialized cells. The over expression of certain genes in brain cells has been linked to neurodegenerative diseases such as Alzheimer’s and Down syndrome. These DNA “cubes” could be engineered to release their drug in the presence of one of these genes. Continued understanding of cellular gene expression could lead to the ability to target specific diseases with DNA “cubes”. The shortcomings of these DNA “cubes” are their stability. These DNA “cubes” would need to be extremely stable in order to effectively deliver their drug to the targeted cells. Researchers will most likely need to combine these DNA “cubes” with other drug delivery techniques in order to better ensure that the DNA “cubes” do not prematurely release their drugs. This is critically important due to the fact that certain drugs could have adverse effects if released into the wrong cellular environment. DNA “cubes” are an innovative and exciting discovery for drug delivery and disease treatment.

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  2. It is so amazing to see how unique we were created. The fact that are bodies are major defense machines on their own is awe-striking enough, but also the ways in which they can respond to things like drugs is also incredible. From a Christian perspective, it really is a puzzle; is dependency on man made items such as pharmaceutical drugs considered acceptable. Although it is important to fully trust in the Lord, He has clearly designed our bodies (and our minds) to react in ways that are incredibly beneficial. To continuously discover all the any "duties" of the body is also quite interesting. From other classes we have learned that DNA is a gene store house that facilitates protein production, it is what makes us different from everyone else (accept a twin). DNA has been studied in great detail since before Watson and Crick and scientists are continuously learning more of its handy features such as the stability and/or reactivity with the environment. The human body is so irreducibly complex, it just amazes me how perfectly we were created.

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  3. This article is really interesting! What a great technological advance to medicinal chemistry! I am a sucker for nanotechnology, but this is over the top because researchers have figured out a way to engage neighboring DNA cubes in an intermolecular ‘handshake’, resulting in a dimer. This forms a monodisperse micelle within a DNA nanostructure, which includes small molecules and releases them by DNA recognition.
    Much can be done with this technology, like the development of better drugs.

    I found another article (http://www.sciencedaily.com/releases/2014/02/140207083828.htm) that describes a breakthrough in artificially linked DNA that was created by joining oligonucleotides using click chemistry, which is a chemistry that mimics nature to generate substances quickly and reliably. The new study demonstrated that there is an error-free way to transcribe human cells. It is exciting to see what others are working on in the scientific development of new and effective treatments!

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  4. Emiene Amali-AdekwuMarch 27, 2016 at 5:49 PM

    It's amazing to read about all the new developments scientists come up with. Whether its brand new technology or novel ways to adapt and modify what we already do, the scientific world is constantly moving forward. I especially enjoyed reading about this new technology because it reminded me of some things we discussed in my Bioethics class. When we begin to talk about introducing nucleic acids as a means of treatment, it is important to account for the body's response to foreign genetic material. Whether it be viruses or bacteria or even cancer cells, our bodies have been programmed to consider most foreign DNA or RNA as threats to normal function. To address prospective issues in this area, I would expect the scientists to turn to the promising field of personalized medicine. When I took Bioethics, we discussed the possibilities of creating drugs that would work specifically for each patient. These drugs would be tailored to their immune systems and would thus reduce the likelihood of rejection or adverse side effects. In this case, the scientists might create DNA cages that the body's immune system would recognize as friendly or personal and not destroy. While it might prove highly costly and effort intensive to create specific nano cages for every cancer patient exposed to this treatment, I do believe it would be more effective than generic ones in the long run.
    Furthermore, this research also raises another question for me. I worry about the availability of this delivery process in vivo. In medicinal chemistry, we have been discussing the roles hydrophobicity and lipophilicity play in drug availability, and even though it seems these scientists have accounted for the binding of the drug to the DNA cage via a lipophilic core, I worry about the external component of this nanostructure. DNA is negatively charged and while this might help to increase the cube's solubility in the surrounding aqueous environment, it might prove difficult to get this charged molecule through the lipid membrane. On the other hand, I guess they have accounted for this by making the cubes extremely tiny. Hopefully, the size of these compounds would be enough to counteract the problems posed by the charge. Nonetheless, this research is ripe with potential and I look forward to learning more about it.

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  5. Nanotechnology seems to be on a great rise throughout this decade. Greater than 100 nations took part in research involving such.(1) From research involving using viruses and magnets to treat cancer, or it is amazing to see the creativity emerging from scientists in the hopes of overcoming diseases and disorders. In regards to this specific method, though, it would be interesting to understand why and how the DNA works site-specifically. How exactly does it match to a specific place within the body, and how would it “know” when and how to release the contents inside?

    1. A statistical report on nanotechnology research publications. StatNano. http://statnano.com/news/57667. Published February 26, 2017. Accessed March 19, 2017.

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