scholarly journals DNA density-dependent uptake of DNA origami-based two-or three-dimensional nanostructures by immune cells

Nanoscale ◽  
2020 ◽  
Vol 12 (27) ◽  
pp. 14818-14824 ◽  
Author(s):  
Tatsuoki Maezawa ◽  
Shozo Ohtsuki ◽  
Kumi Hidaka ◽  
Hiroshi Sugiyama ◽  
Masayuki Endo ◽  
...  

Using DNA nanostructures with almost identical molecular weight and structural flexibility, this work clearly showed that compactly packaged DNA nanostructures with high DNA density are suitable for the delivery to immune cells.

Nanoscale ◽  
2021 ◽  
Author(s):  
Nicole Weizenmann ◽  
Gerda Scheidgen-Kleyboldt ◽  
Jingjing Ye ◽  
Cordula Bärbel Krause ◽  
Dominik Kauert ◽  
...  

Within the field of DNA nanotechnology, numerous methods were developed to produce complex two- and three-dimensional DNA nanostructures for many different emerging applications. These structures typically suffer from a low...


Minerals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 213
Author(s):  
Hamid Ait Said ◽  
Hassan Noukrati ◽  
Hicham Ben Youcef ◽  
Ayoub Bayoussef ◽  
Hassane Oudadesse ◽  
...  

Three-dimensional hydroxyapatite-chitosan (HA-CS) composites were formulated via solid-liquid technic and freeze-drying. The prepared composites had an apatitic nature, which was demonstrated by X-ray diffraction and Infrared spectroscopy analyses. The impact of the solid/liquid (S/L) ratio and the content and the molecular weight of the polymer on the composite mechanical strength was investigated. An increase in the S/L ratio from 0.5 to 1 resulted in an increase in the compressive strength for HA-CSL (CS low molecular weight: CSL) from 0.08 ± 0.02 to 1.95 ± 0.39 MPa and from 0.3 ± 0.06 to 2.40 ± 0.51 MPa for the HA-CSM (CS medium molecular weight: CSM). Moreover, the increase in the amount (1 to 5 wt%) and the molecular weight of the polymer increased the mechanical strength of the composite. The highest compressive strength value (up to 2.40 ± 0.51 MPa) was obtained for HA-CSM (5 wt% of CS) formulated at an S/L of 1. The dissolution tests of the HA-CS composites confirmed their cohesion and mechanical stability in an aqueous solution. Both polymer and apatite are assumed to work together, giving the synergism needed to make effective cylindrical composites, and could serve as a promising candidate for bone repair in the orthopedic field.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gordon J. Hedley ◽  
Tim Schröder ◽  
Florian Steiner ◽  
Theresa Eder ◽  
Felix J. Hofmann ◽  
...  

AbstractThe particle-like nature of light becomes evident in the photon statistics of fluorescence from single quantum systems as photon antibunching. In multichromophoric systems, exciton diffusion and subsequent annihilation occurs. These processes also yield photon antibunching but cannot be interpreted reliably. Here we develop picosecond time-resolved antibunching to identify and decode such processes. We use this method to measure the true number of chromophores on well-defined multichromophoric DNA-origami structures, and precisely determine the distance-dependent rates of annihilation between excitons. Further, this allows us to measure exciton diffusion in mesoscopic H- and J-type conjugated-polymer aggregates. We distinguish between one-dimensional intra-chain and three-dimensional inter-chain exciton diffusion at different times after excitation and determine the disorder-dependent diffusion lengths. Our method provides a powerful lens through which excitons can be studied at the single-particle level, enabling the rational design of improved excitonic probes such as ultra-bright fluorescent nanoparticles and materials for optoelectronic devices.


Polymers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 295
Author(s):  
Stephanie E. Doyle ◽  
Lauren Henry ◽  
Ellen McGennisken ◽  
Carmine Onofrillo ◽  
Claudia Di Bella ◽  
...  

Degradable bone implants are designed to foster the complete regeneration of natural tissue after large-scale loss trauma. Polycaprolactone (PCL) and hydroxyapatite (HA) composites are promising scaffold materials with superior mechanical and osteoinductive properties compared to the single materials. However, producing three-dimensional (3D) structures with high HA content as well as tuneable degradability remains a challenge. To address this issue and create homogeneously distributed PCL-nanoHA (nHA) scaffolds with tuneable degradation rates through both PCL molecular weight and nHA concentration, we conducted a detailed characterisation and comparison of a range of PCL-nHA composites across three molecular weight PCLs (14, 45, and 80 kDa) and with nHA content up to 30% w/w. In general, the addition of nHA results in an increase of viscosity for the PCL-nHA composites but has little effect on their compressive modulus. Importantly, we observe that the addition of nHA increases the rate of degradation compared to PCL alone. We show that the 45 and 80 kDa PCL-nHA groups can be fabricated via indirect 3D printing and have homogenously distributed nHA even after fabrication. Finally, the cytocompatibility of the composite materials is evaluated for the 45 and 80 kDa groups, with the results showing no significant change in cell number compared to the control. In conclusion, our analyses unveil several features that are crucial for processing the composite material into a tissue engineered implant.


2020 ◽  
Author(s):  
Filip Bošković ◽  
Alexander Ohmann ◽  
Ulrich F. Keyser ◽  
Kaikai Chen

AbstractThree-dimensional (3D) DNA nanostructures built via DNA self-assembly have established recent applications in multiplexed biosensing and storing digital information. However, a key challenge is that 3D DNA structures are not easily copied which is of vital importance for their large-scale production and for access to desired molecules by target-specific amplification. Here, we build 3D DNA structural barcodes and demonstrate the copying and random access of the barcodes from a library of molecules using a modified polymerase chain reaction (PCR). The 3D barcodes were assembled by annealing a single-stranded DNA scaffold with complementary short oligonucleotides containing 3D protrusions at defined locations. DNA nicks in these structures are ligated to facilitate barcode copying using PCR. To randomly access a target from a library of barcodes, we employ a non-complementary end in the DNA construct that serves as a barcode-specific primer template. Readout of the 3D DNA structural barcodes was performed with nanopore measurements. Our study provides a roadmap for convenient production of large quantities of self-assembled 3D DNA nanostructures. In addition, this strategy offers access to specific targets, a crucial capability for multiplexed single-molecule sensing and for DNA data storage.


2019 ◽  
Author(s):  
Helen L. Miller ◽  
Sonia Contera ◽  
Adam J.M. Wollman ◽  
Adam Hirst ◽  
Katherine E. Dunn ◽  
...  

AbstractIntercalation of drug molecules into synthetic DNA nanostructures formed through self-assembled origami has been postulated as a valuable future method for targeted drug delivery. This is due to the excellent biocompatibility of synthetic DNA nanostructures, and high potential for flexible programmability including facile drug release into or near to target cells. Such favourable properties may enable high initial loading and efficient release for a predictable number of drug molecules per nanostructure carrier, important for efficient delivery of safe and effective drug doses to minimise non-specific release away from target cells. However, basic questions remain as to how intercalation-mediated loading depends on the DNA carrier structure. Here we use the interaction of dyes YOYO-1 and acridine orange with a tightly-packed 2D DNA origami tile as a simple model system to investigate intercalation-mediated loading. We employed multiple biophysical techniques including single-molecule fluorescence microscopy, atomic force microscopy, gel electrophoresis and controllable damage using low temperature plasma on synthetic DNA origami samples. Our results indicate that not all potential DNA binding sites are accessible for dye intercalation, which has implications for future DNA nanostructures designed for targeted drug delivery.


2020 ◽  
Author(s):  
Jee-Wei Emily Chen ◽  
Jan Lumibao ◽  
Sarah Leary ◽  
Jann N. Sarkaria ◽  
Andrew J. Steelman ◽  
...  

ABSTRACTBackgroundGlioblastoma is the most common and deadly form of primary brain cancer, accounting for more than thirteen thousand new diagnoses annually in the United States alone. Microglia are the innate immune cells within the central nervous system, acting as a front-line defense against injuries and inflammation via a process that involves transformation from a quiescent to an activated phenotype. Crosstalk between GBM cells and microglia represents an important axis to consider in the development of tissue engineering platforms to examine pathophysiological processes underlying GBM progression and therapy.MethodsThis work used a brain-mimetic hydrogel system to study patient-derived glioblastoma specimens and their interactions with microglia. Here, glioblastoma cells were either cultured alone in 3D hydrogels or in co-culture with microglia in a manner that allowed secretome-based signaling but prevented direct GBM-microglia contact. Patterns of GBM cell invasion were quantified using a three-dimensional spheroid assay. Secretome and transcriptome (via RNAseq) were used to profile the consequences of GBM-microglia interactions.ResultsMicroglia displayed an activated phenotype as a result of GBM crosstalk. Three-dimensional migration patterns of patient derived glioblastoma cells showed invasion was significantly decreased in response to microglia paracrine signaling. Potential molecular mechanisms underlying with this phenotype were identified from bioinformatic analysis of secretome and RNAseq data.ConclusionThe data demonstrate a tissue engineered hydrogel platform can be used to investigate crosstalk between immune cells of the tumor microenvironment related to GBM progression. Such multidimensional models may provide valuable insight to inform therapeutic innovations to improve GBM treatment.


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