De Novo Design of Chemical Stability Near-Infrared Molecular Probes for High-Fidelity Hepatotoxicity Evaluation In Vivo

2019 ◽  
Vol 141 (15) ◽  
pp. 6352-6361 ◽  
Author(s):  
Dan Cheng ◽  
Juanjuan Peng ◽  
Yun Lv ◽  
Dongdong Su ◽  
Dongjie Liu ◽  
...  
Keyword(s):  
Chemical Stability ◽  
Near Infrared ◽  
De Novo ◽  
De Novo Design ◽  
Molecular Probes ◽  
High Fidelity

scholarly journals Self-assembly of large RNA structures: learning from DNA nanotechnology

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Jaimie Marie Stewart ◽  
Elisa Franco
Keyword(s):  
Self Assembly ◽  
De Novo ◽  
Dna Nanotechnology ◽  
De Novo Design ◽  
Dna Nanostructures ◽  
Rna Structures ◽  
Functional Nanostructures ◽  
Rna And Dna ◽  
Unique Chemical

AbstractNucleic acid nanotechnology offers many methods to build self-assembled structures using RNA and DNA. These scaffolds are valuable in multiple applications, such as sensing, drug delivery and nanofabrication. Although RNA and DNA are similar molecules, they also have unique chemical and structural properties. RNA is generally less stable than DNA, but it folds into a variety of tertiary motifs that can be used to produce complex and functional nanostructures. Another advantage of using RNA over DNA is its ability to be encoded into genes and to be expressed in vivo. Here we review existing approaches for the self-assembly of RNA and DNA nanostructures and specifically methods to assemble large RNA structures. We describe de novo design approaches used in DNA nanotechnology that can be ported to RNA. Lastly, we discuss some of the challenges yet to be solved to build micron-scale, multi stranded RNA scaffolds.

scholarly journals In Vivo Resolution of Multiexponential Decays of Multiple Near-Infrared Molecular Probes by Fluorescence Lifetime-Gated Whole-Body Time-Resolved Diffuse Optical Imaging

2007 ◽  
Vol 6 (4) ◽  
pp. 7290.2007.00020 ◽  
Author(s):  
Walter Akers ◽  
Frederic Lesage ◽  
Dewey Holten ◽  
Samuel Achilefu
Keyword(s):  
Optical Imaging ◽  
Fluorescence Lifetime ◽  
Fluorescence Intensity ◽  
Near Infrared ◽  
Molecular Probes ◽  
Whole Body ◽  
Diffuse Optical Imaging ◽  
Fluorescence Lifetimes ◽  
Time Resolved

The biodistribution of two near-infrared fluorescent agents was assessed in vivo by time-resolved diffuse optical imaging. Bacteriochlorophyll a (BC) and cypate-glysine-arginine-aspartic acid-serine-proline-lysine-OH (Cyp-GRD) were administered separately or combined to mice with subcutaneous xenografts of human breast adenocarcinoma and slow-release estradiol pellets for improved tumor growth. The same excitation (780 nm) and emission (830 nm) wavelengths were used to image the distinct fluorescence lifetime distribution of the fluorescent molecular probes in the mouse cancer model. Fluorescence intensity and lifetime maps were reconstructed after raster-scanning whole-body regions of interest by time-correlated single-photon counting. Each captured temporal point-spread function (TPSF) was deconvolved using both a single and a multiexponental decay model to best determine the measured fluorescence lifetimes. The relative signal from each fluorophore was estimated for any region of interest included in the scanned area. Deconvolution of the individual TPSFs from whole-body fluorescence intensity scans provided corresponding lifetime images for comparing individual component biodistribution. In vivo fluorescence lifetimes were determined to be 0.8 ns (Cyp-GRD) and 2 ns (BC). This study demonstrates that the relative biodistribution of individual fluorophores with similar spectral characteristics can be compartmentalized by using the time-domain fluorescence lifetime gating method.

scholarly journals Deep learning for in vivo near-infrared imaging

2020 ◽  
Vol 118 (1) ◽  
pp. e2021446118
Author(s):  
Zhuoran Ma ◽  
Feifei Wang ◽  
Weizhi Wang ◽  
Yeteng Zhong ◽  
Hongjie Dai
Keyword(s):  
Deep Learning ◽  
Light Scattering ◽  
Near Infrared ◽  
Infrared Imaging ◽  
Imaging Modality ◽  
Molecular Probes ◽  
Clinical Diagnostics ◽  
Light Sheet Microscopy ◽  
Lymph Node Imaging

Detecting fluorescence in the second near-infrared window (NIR-II) up to ∼1,700 nm has emerged as a novel in vivo imaging modality with high spatial and temporal resolution through millimeter tissue depths. Imaging in the NIR-IIb window (1,500–1,700 nm) is the most effective one-photon approach to suppressing light scattering and maximizing imaging penetration depth, but relies on nanoparticle probes such as PbS/CdS containing toxic elements. On the other hand, imaging the NIR-I (700–1,000 nm) or NIR-IIa window (1,000–1,300 nm) can be done using biocompatible small-molecule fluorescent probes including US Food and Drug Administration-approved dyes such as indocyanine green (ICG), but has a caveat of suboptimal imaging quality due to light scattering. It is highly desired to achieve the performance of NIR-IIb imaging using molecular probes approved for human use. Here, we trained artificial neural networks to transform a fluorescence image in the shorter-wavelength NIR window of 900–1,300 nm (NIR-I/IIa) to an image resembling an NIR-IIb image. With deep-learning translation, in vivo lymph node imaging with ICG achieved an unprecedented signal-to-background ratio of >100. Using preclinical fluorophores such as IRDye-800, translation of ∼900-nm NIR molecular imaging of PD-L1 or EGFR greatly enhanced tumor-to-normal tissue ratio up to ∼20 from ∼5 and improved tumor margin localization. Further, deep learning greatly improved in vivo noninvasive NIR-II light-sheet microscopy (LSM) in resolution and signal/background. NIR imaging equipped with deep learning could facilitate basic biomedical research and empower clinical diagnostics and imaging-guided surgery in the clinic.

scholarly journals Designed for life: biocompatible de novo designed proteins and components

2018 ◽  
Vol 15 (145) ◽  
pp. 20180472 ◽  
Author(s):  
Katie J. Grayson ◽  
J. L. Ross Anderson
Keyword(s):  
Protein Design ◽  
De Novo ◽  
Building Blocks ◽  
De Novo Design ◽  
Biochemical Processes ◽  
Designed Proteins ◽  
De Novo Protein Design ◽  
Protein Molecules ◽  
And Function

A principal goal of synthetic biology is the de novo design or redesign of biomolecular components. In addition to revealing fundamentally important information regarding natural biomolecular engineering and biochemistry, functional building blocks will ultimately be provided for applications including the manufacture of valuable products and therapeutics. To fully realize this ambitious goal, the designed components must be biocompatible, working in concert with natural biochemical processes and pathways, while not adversely affecting cellular function. For example, de novo protein design has provided us with a wide repertoire of structures and functions, including those that can be assembled and function in vivo . Here we discuss such biocompatible designs, as well as others that have the potential to become biocompatible, including non-protein molecules, and routes to achieving full biological integration.

scholarly journals De Novo Design of Polymeric Carrier to Photothermally Release Singlet Oxygen for Hypoxic Tumor Treatment

Research ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Tianci Huang ◽  
Menglong Zhao ◽  
Qi Yu ◽  
Zheng Feng ◽  
Mingjuan Xie ◽  
...  
Keyword(s):  
Singlet Oxygen ◽  
De Novo ◽  
Inhibitory Effect ◽  
De Novo Design ◽  
Tumor Treatment ◽  
Polymer Carrier ◽  
Hypoxic Environment ◽  
Therapeutic Platform

Intratumoral hypoxia extremely limits the clinic applications of photodynamic therapy (PDT). Endoperoxides allow thermally releasing singlet oxygen (1O2) in a defined quantity and offer promising opportunities for oxygen-independent PDT treatment of hypoxic tumors. However, previous composite systems by combining endoperoxides with photothermal reagents may result in unpredicted side effects and potential harmful impacts during therapy in vivo. Herein, we de novo design an all-in-one polymer carrier, which can photothermally release 1O2. The strategy has been demonstrated to effectively enhance the production of 1O2 and realize the photodamage in vitro, especially in hypoxic environment. Additionally, the polymer carrier accumulates into tumor after intravenous injection via the enhanced permeation and retention effects and accelerates the oxygen-independent generation of 1O2 in tumors. The oxidative damage results in good inhibitory effect on tumor growth. Realization of the strategy in vivo paves a new way to construct photothermal-triggered oxygen-independent therapeutic platform for clinical applications.

102Diagnosis of coronary plaque rupture, plaque erosion, and calcified nodule by using near-infrared spectroscopy intravascular ultrasound

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Terada ◽  
T Kubo ◽  
Y Matsuo ◽  
Y Ino ◽  
H Kitabata ◽  
...  
Keyword(s):  
Infrared Spectroscopy ◽  
Intravascular Ultrasound ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
De Novo ◽  
Plaque Rupture ◽  
High Specificity ◽  
Plaque Erosion ◽  
Plaque Ulceration

Abstract Objectives This study sought to investigate the ability of near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) to differentiate among plaque rupture (PR), plaque erosion (PE), and calcified nodule (CN) in acute myocardial infarction (AMI) using an optical coherence tomography (OCT) diagnosis as a reference standard. Background In vivo, precise differentiation among PR, PE and CN is a major challenge for intravascular imaging. Methods The study enrolled 156 AMI patients who had a de novo culprit lesion in a native coronary artery. The culprit lesions were assessed by both NIRS-IVUS and OCT. Results OCT identified 112 PR, 29 PE, and 15 CN. IVUS-detected plaque ulceration showed a high specificity (100%) to identify OCT-PR although the sensitivity (62%) was intermediate. IVUS-detected convex calcium showed a high sensitivity (93%) and specificity (100%) to identify OCT-CN. In NIRS, the maximum lipid core burden index in 4 mm (maxLCBI4mm) was greatest in OCT-PR (values are median [interquartile range]) (671 [530 to 853]), followed by OCT-CN (355 [303 to 432]) and OCT-PE (283 [89 to 357]) (p<0.001). MaxLCBI4mm of <422 was the best cut-off to discriminate OCT-PE from OCT-PR and OCT-CN. The NIRS-IVUS classification algorithm using plaque ulceration, convex calcium, and maxLCBI4mm <422 showed a sensitivity and specificity of 96% and 95% for identifying OCT-PR, 93% and 95% for OCT-PE, and 93% and 100% for OCT-CN, respectively. NIRS-IVUS classification algorism Conclusion Lipid component assessed by NIRS-IVUS was different among OCT-PR, OCT-PE and OCT-CN. The NIRS-IVUS classification algorism was highly sensitive and specific for differentiating these unstable lesion types in AMI. Acknowledgement/Funding None

scholarly journals De novo design of symmetric ferredoxins that shuttle electrons in vivo

2019 ◽  
Vol 116 (29) ◽  
pp. 14557-14562 ◽  
Author(s):  
Andrew C. Mutter ◽  
Alexei M. Tyryshkin ◽  
Ian J. Campbell ◽  
Saroj Poudel ◽  
George N. Bennett ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Electron Transfer ◽  
Gene Duplication ◽  
Sequence Space ◽  
Metabolic Pathway ◽  
De Novo ◽  
Phylogenetic Analyses ◽  
De Novo Design ◽  
Symmetric Molecule

A symmetric origin for bacterial ferredoxins was first proposed over 50 y ago, yet, to date, no functional symmetric molecule has been constructed. It is hypothesized that extant proteins have drifted from their symmetric roots via gene duplication followed by mutations. Phylogenetic analyses of extant ferredoxins support the independent evolution of N- and C-terminal sequences, thereby allowing consensus-based design of symmetric 4Fe-4S molecules. All designs bind two [4Fe-4S] clusters and exhibit strongly reducing midpoint potentials ranging from −405 to −515 mV. One of these constructs efficiently shuttles electrons through a designed metabolic pathway inEscherichia coli. These finding establish that ferredoxins consisting of a symmetric core can be used as a platform to design novel electron transfer carriers for in vivo applications. Outer-shell asymmetry increases sequence space without compromising electron transfer functionality.

scholarly journals De Novo-Designed Near-Infrared Nanoaggregates for Super-Resolution Monitoring of Lysosomes in Cells, in Whole Organoids, and in Vivo

ACS Nano ◽  
2019 ◽  
Vol 13 (12) ◽  
pp. 14426-14436 ◽  
Author(s):  
Hongbao Fang ◽  
Shankun Yao ◽  
Qixin Chen ◽  
Chunyan Liu ◽  
Yuqi Cai ◽  
...  
Keyword(s):  
Near Infrared ◽  
De Novo ◽  
Super Resolution ◽  
In Cells
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