DNA Origami: Daunorubicin‐Loaded DNA Origami Nanostructures Circumvent Drug‐Resistance Mechanisms in a Leukemia Model (Small 3/2016)

Abstract

DNA origami “Trojan horse” nanostructures provide an effective delivery approach to circumvent drug resistance in leukemia cells. These 100 nanometer delivery vehicles, described on page 308 by C. E. Castro and co‐workers, are easily fabricated in 10 min and can be precisely loaded with commonly used anthracycline chemotherapeutic drugs. Drug‐loaded DNA origami nanostructures enter cells via endocytosis, allowing the drug to bypass defenses in the cell membrane that are effective against free drug. This approach leads to larger amounts of drug in cells, which is later released due to decreasing pH and enzymatic degradation, ultimately improving drug efficacy.

Critical review of nucleic acid nanotechnology to identify gaps and inform a strategy for accelerated clinical translation

“…Taken together, these recent strategies demonstrate the ability to co-formulate multiple targeting and gene therapeutic modalities, as well as endow specific triggering and responsive properties in cellular pathways of interest. While significant fundamental work is still required to better characterize the efficacy of these formulations in vivo compared with standard, competing delivery technologies such as LNPs, together with a growing list of other therapeutic formulations and capabilities [29] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , NANPs offer promising avenues for further research into potentially clinically relevant modalities.

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Fluorous-Directed Assembly of DNA Origami Nanostructures

“…The DNA origami method uses Watson–Crick base-pairing to direct the folding of a long single-stranded piece of DNA (ssDNA) (the scaffold) with a set of complementary oligodeoxyribonucleotide (ODN) strands (staples), whose rational design leads to the creation of intricate two- and three-dimensional nanostructures. − The modularity of DNA origami and the accessibility of a defined ssDNA template makes this approach one of the most versatile methods to predictably and reproducibly prepare nanostructures in the 100 nm regime. Furthermore, the incorporation of recognition elements in ODN staples permits the spatial arrangement of components with subnanometer precision, providing additional functionality for applications spanning biosensing, drug delivery, and the fabrication of photonic devices. − …”

Protein-Functionalized DNA Nanostructures as Tools to Control Transcription in Zebrafish Embryos

“…[12][13][14] DONs are functional as immune-activating programmable adjuvants, [15,16] and they can be used as drug-delivery vehicles to circumvent drug resistance. [17][18][19][20] These studies have suggested that intracellular DON uptake is usually dependent on endocytosis. [18] Furthermore, DONs can bind to the outside of the cells to stimulate cellular transmembrane receptors.…”

“…For instance, it has been demonstrated that DONs are stable reagents under cell culturing conditions . DONs are functional as immune‐activating programmable adjuvants, and they can be used as drug‐delivery vehicles to circumvent drug resistance . These studies have suggested that intracellular DON uptake is usually dependent on endocytosis .…”