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Will complex, folded synthetic DNA molecules one day serve as capsules to deliver drugs to cancer cells?
July 17, 2017|
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August 16, 2017
How to assume a particular folding pattern to become a particular drug?
August 24, 2017
The author correctly points out that "While there are no DNA nanostructure–based drug delivery carriers yet in clinical trials, research towards this goal is being pursued."
Anyone examining activities targeted drug delivery research and development over the last 4-5 decades is likely to come to a conclusion that the whole concept of a "Trojan horse" is flawed. Various material - polymers, particles, colloids, liposomes, dendrimers, etc. have been shown to do much the same as has been so far shown with DNA constructs - delivery of particles to various body sites, and the release of the loaded drug there in vitro and in animal models. However, clinical efficacy of such approach has been hard to come by, with the only successful outcomes being obtained with therapeutic antibodies (but even in this case the outcome is by no means without defficiencies).
One key consideration that is almost always being ignored is the nature and pharmacokinetics of the drug itself. Releasing a drug "near" the target often leads to removal of the drug faster than it can accumulate at the site to reach pharmacologically effective concentration. Hence, distribution of the drug away from the site negates its delivery.
New paradigm for drug delivery should recognize it and should involve 1) constructing new drugs that bind specifically to unique molecular features of disease target (hopefully such disease-target features will be identified as a result of current research initiatives (PMI, AMP, etc.), and 2) accepting a new manner of selecting drugs for targeting with pharmacokinetic properties that will result in drugs' longer residence at target sites.
On a positive side, I see a potential use of "DNA Origami" and similar DNA constructs for delivering "therapeutic DNA fragments" to sites of disease provided that DNA constructs can be uniquely recognized by diseased cell and the delivered DNA fragments have the desired therapeutic effect.