scholarly journals Targeted Molecular Imaging Using Aptamers in Cancer

2018 ◽  
Vol 11 (3) ◽  
pp. 71 ◽  
Author(s):  
Sorah Yoon ◽  
John Rossi
Keyword(s):  
Wide Spectrum ◽  
Rna Aptamers ◽  
Tissue Imaging ◽  
Live Cells ◽  
Target Cells ◽  
New Class ◽  
Non Invasive ◽  
Resolution Imaging ◽  
Tissue Specimens

Imaging is not only seeing, but also believing. For targeted imaging modalities, nucleic acid aptamers have features such as superior recognition of structural epitopes and quick uptake in target cells. This explains the emergence of an evolved new class of aptamers into a wide spectrum of imaging applications over the last decade. Genetically encoded biosensors tagged with fluorescent RNA aptamers have been developed as intracellular imaging tools to understand cellular signaling and physiology in live cells. Cancer-specific aptamers labeled with fluorescence have been used for assessment of clinical tissue specimens. Aptamers conjugated with gold nanoparticles have been employed to develop innovative mass spectrometry tissue imaging. Also, use of chemically conjugated cancer-specific aptamers as probes for non-invasive and high-resolution imaging has been transformative for in vivo imaging in multiple cancers.

scholarly journals A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Soudeh Moghadasi ◽  
Marischa Elveny ◽  
Heshu Sulaiman Rahman ◽  
Wanich Suksatan ◽  
Abduladheem Turki Jalil ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Ethical Issues ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Experimental Models ◽  
Live Cells ◽  
Target Cells ◽  
Intercellular Interaction ◽  
Micro Rnas

AbstractRecently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

scholarly journals High-resolution in vivo imaging of mouse brain through the intact skull

2015 ◽  
Vol 112 (30) ◽  
pp. 9236-9241 ◽  
Author(s):  
Jung-Hoon Park ◽  
Wei Sun ◽  
Meng Cui
Keyword(s):  
High Resolution ◽  
Biological Tissue ◽  
Morphological Changes ◽  
Complex Refractive Index ◽  
Incident Light ◽  
Multiphoton Microscopy ◽  
Current Method ◽  
Tissue Imaging ◽  
Resolution Imaging

Multiphoton microscopy is the current method of choice for in vivo deep-tissue imaging. The long laser wavelength suffers less scattering, and the 3D-confined excitation permits the use of scattered signal light. However, the imaging depth is still limited because of the complex refractive index distribution of biological tissue, which scrambles the incident light and destroys the optical focus needed for high resolution imaging. Here, we demonstrate a wavefront-shaping scheme that allows clear imaging through extremely turbid biological tissue, such as the skull, over an extended corrected field of view (FOV). The complex wavefront correction is obtained and directly conjugated to the turbid layer in a noninvasive manner. Using this technique, we demonstrate in vivo submicron-resolution imaging of neural dendrites and microglia dynamics through the intact skulls of adult mice. This is the first observation, to our knowledge, of dynamic morphological changes of microglia through the intact skull, allowing truly noninvasive studies of microglial immune activities free from external perturbations.

scholarly journals Direct focus sensing and shaping for high-resolution multi-photon imaging in deep tissue

2021 ◽  
Author(s):  
Jianan Qu ◽  
ZHONGYA QIN ◽  
ZHENTAO SHE ◽  
CONGPING CHEN ◽  
WANJIE WU ◽  
...  
Keyword(s):  
High Resolution ◽  
Adaptive Optics ◽  
High Sensitivity ◽  
Deep Tissue ◽  
Non Invasive ◽  
Mouse Cortex ◽  
Intact Brain ◽  
Resolution Imaging

High-resolution optical imaging of deep tissue in-situ such as the living brain is fundamentally challenging because of the aberration and scattering of light. In this work, we develop an innovative adaptive optics three-photon microscope based on direct focus sensing and shaping that can accurately measure and effectively compensate for both low- and high-order specimen-induced aberrations and recover near-diffraction-limited performance at depth. A conjugate adaptive optics configuration with remote focusing enables in vivo imaging of fine neuronal structures in the mouse cortex through the intact skull up to a depth of 750 um below pia, making high-resolution microscopy in cortex near non-invasive. Functional calcium imaging with high sensitivity and accuracy, and high-precision laser-mediated microsurgery through the intact skull were demonstrated. Moreover, we also achieved in vivo high-resolution imaging of the deep cortex and subcortical hippocampus up to 1.1 mm below pia within the intact brain.

scholarly journals A mesh microelectrode array for non-invasive electrophysiology within neural organoids

2020 ◽  
Author(s):  
Matthew McDonald ◽  
David Sebinger ◽  
Lisa Brauns ◽  
Laura Gonzalez-Cano ◽  
Yotam Menuchin-Lasowski ◽  
...  
Keyword(s):  
Microelectrode Array ◽  
Single Cells ◽  
Three Dimensional ◽  
Microelectrode Arrays ◽  
Polymer Scaffolds ◽  
Neural Models ◽  
New Class ◽  
Non Invasive

AbstractOrganoids are emerging in vitro models of human physiology. Neural models require the evaluation of functional activity of single cells and networks, which is best measured by microelectrode arrays. The characteristics of organoids clash with existing in vitro or in vivo microelectrode arrays. With inspiration from implantable mesh electronics and growth of organoids on polymer scaffolds, we fabricated suspended hammock-like mesh microelectrode arrays for neural organoids. We have demonstrated the growth of organoids enveloping these meshes, their cultivation for at least nine months, and could measure spontaneous electrical activity within organoids. Our concept should enable a new class of microelectrode arrays for in vitro models of three-dimensional electrically active tissue.

scholarly journals Characterization of a DNA Aptamer for Ovarian Cancer Clinical Tissue Recognition and in Vivo Imaging

2018 ◽  
Vol 51 (6) ◽  
pp. 2564-2574 ◽  
Author(s):  
Fengjie Li ◽  
Qian Wang ◽  
Hui Zhang ◽  
Tanggang Deng ◽  
Peifu Feng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dissociation Constants ◽  
Target Function ◽  
Dna Aptamer ◽  
Tissue Imaging ◽  
Ovarian Cancer Cells ◽  
Target Cells ◽  
Microscope Imaging ◽  
Cancer Tissues

Backgrounds/Aims: Ovarian cancer is the most lethal gynaecologic malignancy and is difficult to detect early. The inefficient early diagnosis of ovarian cancer is the main contributor to its high mortality rate. Aptamers, as chemical antibodies, are single-stranded DNA or RNA oligonucleotides that target cells or molecules with high affinity. Methods: Binding ability of R13 was measured by flow cytometry analysis. Stability of R13 was tested in blood serum of an ovarian cancer patient. Internalization of R13 was verified by confocal microscope imaging. 80 cases ovarian cancer tissues, 10 cases normal ovary tissues in a microarray and 6 fallopian tube tissues were prepared for this study. R13’s target ability was further confirmed in vivo tumor models in NOD/SCID mice. Results: In this study, we found aptamer R13 bound to ovarian cancer cells with dissociation constants in the nanomolar range. Moreover, these results were further confirmed by tissue imaging. Next we demonstrated that the targets of R13 are membrane proteins and that its internalization occurs in a caveolae-mediated and clathrin-mediated manner. The target function of R13 was determined by imaging A2780 tumours in mouse models. Conclusion: These findings suggest that R13 is a promising novel tool to diagnose and deliver drugs to treat ovarian cancer.

scholarly journals A far-red fluorescent chemogenetic reporter for in vivo molecular imaging

2020 ◽  
Author(s):  
Chenge Li ◽  
Alison G. Tebo ◽  
Marion Thauvin ◽  
Marie-Aude Plamont ◽  
Michel Volovitch ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Zebrafish Embryo ◽  
Tissue Imaging ◽  
Live Cells ◽  
Protein Protein Interactions ◽  
Deep Tissue ◽  
Red Fluorescence ◽  
Genetic Encoding ◽  
Deep Tissue Imaging

AbstractFar-red emitting fluorescent labels are highly desirable for spectral multiplexing and deep tissue imaging. Here, we describe the generation of frFAST (far-red Fluorescence Activating and absorption Shifting Tag), a 14-kDa monomeric protein that forms a bright far-red fluorescent assembly with (4-hydroxy-3-methoxy-phenyl)allylidene rhodanine (HPAR-3OM). As HPAR-3OM is essentially non-fluorescent in solution and in cells, frFAST can be imaged with high contrast in presence of free HPAR-3OM, which allowed the rapid and efficient imaging of frFAST fusions in live cells, zebrafish embryo/larvae and chicken embryo. Beyond enabling genetic encoding of far-red fluorescence, frFAST allowed the design of a far-red chemogenetic reporter of protein-protein interactions, demonstrating its great potential for the design of innovative far-red emitting biosensors.

scholarly journals Tau avoids the GTP cap at growing microtubule plus ends

2020 ◽  
Author(s):  
Brian T. Castle ◽  
Kristen M. McKibben ◽  
Elizabeth Rhoades ◽  
David J. Odde
Keyword(s):  
Neural Development ◽  
Neurological Disease ◽  
Live Cells ◽  
Cellular Functions ◽  
Microtubule Associated Proteins ◽  
New Class ◽  
Associated Proteins ◽  
Microtubule Growth

AbstractPlus-end tracking proteins (+TIPs) are a group of proteins that associate with the growing end of microtubules and mediate important cellular functions including neural development and cell division. Work in recent years has shown that the majority of +TIPs are directed to the plus-end through a family of end binding proteins (EBs), which preferentially bind the stabilizing cap of GTP-tubulin present during microtubule growth, versus weaker binding to GDP-tubulin in the proximal microtubule. One question yet to be addressed is whether there may exist other microtubule associated proteins (MAPs) that preferentially bind specific nucleotide states of tubulin. Here we report that the neuronal MAP tau, which is enriched in axons where it promotes microtubule growth and bundling, preferentially binds GDP-tubulin (KD = 0.26 µM) over GMPCPP-tubulin (KD = 1.1 µM) in vitro as well as GTP-tubulin at the tips of growing microtubules in vitro and in vivo. This nucleotide preference causes tau binding to lag behind the growing microtubule plus-end by about 100-200 nm both in vitro and in live cells. Thus, tau is a microtubule tip avoiding protein, establishing a new class of tip avoiding MAPs, and acts primarily by suppressing microtubule shortening rather than promoting growth. We speculate that neurological disease-relevant tau mutations may exert their phenotype by their failure to properly recognize GDP-tubulin, thus displacing +TIPs, such as EB3, and their associated activities into abnormal locations in the neuron.

scholarly journals Deep brain fluorescence imaging with minimally invasive ultra-thin optical fibers

2017 ◽  
Author(s):  
Shay Ohayon ◽  
Antonio M. Caravaca-Aguirre ◽  
Rafael Piestun ◽  
James J. DiCarlo
Keyword(s):  
Optical Fibers ◽  
Neural Activity ◽  
Brain Regions ◽  
Volumetric Imaging ◽  
Non Invasive ◽  
Cellular Resolution ◽  
Calcium Indicator ◽  
Acquisition Speed ◽  
Resolution Imaging

AbstractA major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well-defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive (surface) multiphoton approaches1,2 for deep (>2mm) structures, while Gradient Refreactive Index (GRIN) endoscopes2–4 are thick and cause significant damage upon insertion. Here, we demonstrate a novel microendoscope to image neural activity at arbitrary depths via an ultrathin multimode optical fiber (MMF) probe that is 5-10X thinner than commercially available microendoscopes. We demonstrate micron-scale resolution, multispectral and volumetric imaging. In contrast to previous approaches1,5–8 we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator. Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions.

scholarly journals In Vivo Cell Tracking Using PET: Opportunities and Challenges for Clinical Translation in Oncology

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4042
Author(s):  
Laura M. Lechermann ◽  
Doreen Lau ◽  
Bala Attili ◽  
Luigi Aloj ◽  
Ferdia A. Gallagher
Keyword(s):  
Cell Tracking ◽  
Ex Vivo ◽  
Wide Spectrum ◽  
Personalised Medicine ◽  
Target Cells ◽  
Cell Therapies ◽  
Detection And Tracking ◽  
Positron Emission ◽  
Cancer Models

Cell therapy is a rapidly evolving field involving a wide spectrum of therapeutic cells for personalised medicine in cancer. In vivo imaging and tracking of cells can provide useful information for improving the accuracy, efficacy, and safety of cell therapies. This review focuses on radiopharmaceuticals for the non-invasive detection and tracking of therapeutic cells using positron emission tomography (PET). A range of approaches for imaging therapeutic cells is discussed: Direct ex vivo labelling of cells, in vivo indirect labelling of cells by utilising gene reporters, and detection of specific antigens expressed on the target cells using antibody-based radiopharmaceuticals (immuno-PET). This review examines the evaluation of PET imaging methods for therapeutic cell tracking in preclinical cancer models, their role in the translation into patients, first-in-human studies, as well as the translational challenges involved and how they can be overcome.

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