DNA Nanocarriers: Programmed to Deliver

Madhanagopal, Bharath Raj; Zhang, Shunqing; Demirel, Esra; Wady, Heitham; Chandrasekaran, Arun Richard

doi:10.1016/j.tibs.2018.09.010

Cited by 112 publications

(91 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, densely coating the outer surface of DNA brick nanostructures with dendritic oligonucleotides prevents nuclease digestion.DNA nanotechnology enables the synthesis of rationally designed DNA nanostructures of arbitrary geometric configuration, [1] and such molecular-scale nanodevices can be used in biomedical applications, driving the field towards programmable and customizable nanomedicine. [2,3] Examples of DNA nanocages, [4,5] capsules, [6] and carriers [7] have been studied as delivery vehicles or diagnostic devices for drug delivery, cancer treatment, and immunotherapy. [2,7] Nevertheless, more recent literature highlights the importance of the structural stability of DNA-based materials under physiological conditions when using them in vitro and/or in vivo.…”

mentioning

confidence: 99%

“…[2,3] Examples of DNA nanocages, [4,5] capsules, [6] and carriers [7] have been studied as delivery vehicles or diagnostic devices for drug delivery, cancer treatment, and immunotherapy. [2,7] Nevertheless, more recent literature highlights the importance of the structural stability of DNA-based materials under physiological conditions when using them in vitro and/or in vivo. [8][9][10][11] This is due to two main factors involved in degradation of DNA nanostructures upon exposure to biological conditions: i) denaturation caused by low divalent cation concentration (physiological salt concentration approximately 0.04-0.8 mm MgCl 2 ), and ii) digestion caused by the presence of nucleases.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Enhancing Biocompatible Stability of DNA Nanostructures Using Dendritic Oligonucleotides and Brick Motifs

Kim

Yin

2019

Angew Chem Int Ed

View full text Add to dashboard Cite

The use of DNA‐based nanomaterials in biomedical applications is continuing to grow, yet more emphasis is being put on the need for guaranteed structural stability of DNA nanostructures in physiological conditions. Various methods have been developed to stabilize DNA origami against low concentrations of divalent cations and the presence of nucleases. However, existing strategies typically require the complete encapsulation of nanostructures, which makes accessing the encased DNA strands difficult, or chemical modification, such as covalent crosslinking of DNA strands. We present a stabilization method involving the synthesis of DNA brick nanostructures with dendritic oligonucleotides attached to the outer surface. We find that nanostructures assembled from DNA brick motifs remain stable against denaturation without any chemical modifications. Furthermore, densely coating the outer surface of DNA brick nanostructures with dendritic oligonucleotides prevents nuclease digestion.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Enhancing Biocompatible Stability of DNA Nanostructures Using Dendritic Oligonucleotides and Brick Motifs

Kim

Yin

2019

Angew Chem Int Ed

View full text Add to dashboard Cite

show abstract

“…This structure had pronounced immunostimulation through the TLR‐9 pathway and endosomal targeting . DNA origami–based nanostructures offer programmable and flexible designs, making them promising drug‐delivery vehicles for various biomedical and immunoengineering applications …”

Section: Man‐made Dna Materials For Immunoengineeringmentioning

confidence: 99%

DNA‐Based Biomaterials for Immunoengineering

Maeda

Kojima

Song

et al. 2018

Adv Healthcare Materials

View full text Add to dashboard Cite

of extracellular DNA in tissues and in circulation. [5] Extracellular DNA is capable of engaging with the immune system as depicted in Figure 1; therefore, as synthetic DNA-based biomaterials emerge, their potential immune responses must be considered. DNA sensors are mediators of extracellular DNA immune responses observed in vivo, including cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and toll-like receptors (TLRs). Defining novel DNA sensors and their mechanisms is an active area of investigation. [6] Likewise, the structural and chemical properties of DNA that triggers DNA sensors continue to be uncovered. [6] This review summarizes known DNA interaction modalities with the immune system, the sources of extracellular DNA, and, finally, the relevant and emerging biotechnologies that incorporate DNA molecules. A focus is geared toward innate immune responses and doublestranded DNA (dsDNA). Leveraging the immunomodulatory capacity of DNA enables tailoring materials to initiate specific immune outcomes depending on the application, for instance, priming aggressive immune responses for localized tumor-interfacing biomaterials or immunosuppressive functions to prevent chronic inflammation on implant surfaces. Achieving this requires an improved understanding of the DNA properties, such as backbone chemistry, base pair sequence, charge, and length, that can function as design levers for the immune response. The Role of Extracellular DNA in the Immune ResponseThe immune system is designed to protect the host against infections by distinguishing between self-and non-self motifs, and by identifying pathogen and damage signals. Upon recognition of a "non-self" or foreign molecule, an array of effector functions are triggered and orchestrated by immune cells to achieve pathogen clearance and restore homeostasis. [7] These immunoactivating defense mechanisms include the release of proinflammatory cytokines, immune cell recruitment, programmed cell death, and phagocytosis. Ideally, immunoactivating responses are supplanted by immunosuppressive functions once the pathogen or agonist is resolved. This immune resolution is necessary to coordinate healing and anti-inflammatory functions such as diminished chemokine and cytokine secretion, replacement Man-made DNA materials hold the potential to modulate specific immune pathways toward immunoactivating or immunosuppressive cascades. DNAbased biomaterials introduce DNA into the extracellular environment during implantation or delivery, and subsequently intracellularly upon phagocytosis or degradation of the material. Therefore, the immunogenic functionality of biological and synthetic extracellular DNA should be considered to achieve desired immune responses. In vivo, extracellular DNA from both endogenous and exogenous sources holds immunoactivating functions which can be traced back to the molecular features of DNA, such as sequence and length. Extracellular DNA is recognized as damage-associated molecular patterns (DAMPs), or pathogen-associated mole...

show abstract

“…To succeed as drug delivery vehicles, DNA objects must overcome a major challenge of surviving harsh "in vivo" environments such as blood. 6 Strategies to improve the biostability of DNA structures include polymer coating, viral capsid encapsulation, modified nucleotides and crosslinking. 7 One possibility that has been largely overlooked is that the inherent design of these DNA nanostructures can be altered to change biostability.…”

Section: Introductionmentioning

confidence: 99%

Exceptional biostability of paranemic crossover (PX) DNA, crossover-dependent nuclease resistance, and implications for DNA nanotechnology

Chandrasekaran

Vilcapoma

Dey

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Inherent nanometer-sized features and molecular recognition properties make DNA a useful material in constructing nanoscale objects, with alluring applications in biosensing and drug delivery. However, DNA can be easily degraded by nucleases present in biological fluids, posing a considerable roadblock to realizing the full potential of DNA nanotechnology for biomedical applications. Here we investigated the nuclease resistance and biostability of the multi-stranded motif called paranemic crossover (PX) DNA and discovered a remarkable and previously unreported resistance to nucleases. We show that PX DNA has more than an order of magnitude increased resistance to degradation by DNase I, serum, and urine compared to double stranded DNA. We further demonstrate that the degradation resistance decreases monotonically as DNA crossovers are removed from the structure, suggesting that frequent DNA crossovers disrupt either the binding or catalysis of nucleases or both. These results have important implications for building DNA nanostructures with enhanced biostability, either by adopting PX-based architectures or by carefully engineering crossovers. We contend that such crossover-dependent nuclease resistance could potentially be used to add "tunable biostability" to the many features of DNA nanotechnology.

show abstract

DNA Nanocarriers: Programmed to Deliver

Cited by 112 publications

References 124 publications

Enhancing Biocompatible Stability of DNA Nanostructures Using Dendritic Oligonucleotides and Brick Motifs

Enhancing Biocompatible Stability of DNA Nanostructures Using Dendritic Oligonucleotides and Brick Motifs

DNA‐Based Biomaterials for Immunoengineering

Exceptional biostability of paranemic crossover (PX) DNA, crossover-dependent nuclease resistance, and implications for DNA nanotechnology

Contact Info

Product

Resources

About