Virus-like particles are good nanocarriers for liquid biopsy probes, imaging contrast agents, and anticancer medications

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Contrast Agents ◽  
Liquid Biopsy ◽  
Plasma Proteins ◽  
Tumor Targeting ◽  
Competitive Advantages ◽  
Virus Like Particles ◽  
Delivery Technique ◽  
Cell Affinity ◽  
Targeting Effectiveness

Recent advances in nanotechnology, chemistry, and material science have spurred the development and deployment of virus-mimetic particles. Virus-like particles have several competitive advantages. Virus-like particles are good nanocarriers for liquid biopsy probes, imaging contrast agents, and anticancer medications because of these advantages. Despite these encouraging improvements, virus-mimetic particles still have a number of shortcomings, particularly in vivo immune response and tumor targeting efficiency. The immunogenicity of virus-like particles is reduced to some extent by PEGylation of the viral capsid surface, allowing for passive tumor targeting. PEGylation, on the other hand, causes the ABC phenomenon, which results in the formation of new immune responses. Researchers are currently looking for novel materials with immune camouflage properties to negate the immunostimulatory potential of particles. Although it is projected that altering some types of virus-like particles will increase their targeted internalization, the plasma proteins adsorbed by the particles will diminish particle-target cell affinity. The corona-mediated delivery technique improves in vivo targeting effectiveness and may pave the way for clinical translation of virus-mimetic particles. With quick knowledge renewal of nanoparticle in vivo behaviors and ongoing invention of research methodologies and procedures, virusmimetic nanoparticles are projected to be completely endowed with the twin roles of immune camouflage and tumor targeting, displaying great therapeutic effectiveness.

scholarly journals Functionalized Lanthanide Oxide Nanoparticles for Tumor Targeting, Medical Imaging, and Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1890
Author(s):  
Mohammad Yaseen Ahmad ◽  
Huan Yue ◽  
Tirusew Tegafaw ◽  
Shuwen Liu ◽  
Son Long Ho ◽  
...  
Keyword(s):  
Medical Imaging ◽  
Contrast Agents ◽  
Tumor Targeting ◽  
Imaging Techniques ◽  
Tumor Therapy ◽  
Mri Contrast Agents ◽  
Mri Contrast ◽  
Lanthanide Oxide ◽  
X Ray

Recent progress in functionalized lanthanide oxide (Ln2O3) nanoparticles for tumor targeting, medical imaging, and therapy is reviewed. Among the medical imaging techniques, magnetic resonance imaging (MRI) is an important noninvasive imaging tool for tumor diagnosis due to its high spatial resolution and excellent imaging contrast, especially when contrast agents are used. However, commercially available low-molecular-weight MRI contrast agents exhibit several shortcomings, such as nonspecificity for the tissue of interest and rapid excretion in vivo. Recently, nanoparticle-based MRI contrast agents have become a hot research topic in biomedical imaging due to their high performance, easy surface functionalization, and low toxicity. Among them, functionalized Ln2O3 nanoparticles are applicable as MRI contrast agents for tumor-targeting and nontumor-targeting imaging and image-guided tumor therapy. Primarily, Gd2O3 nanoparticles have been intensively investigated as tumor-targeting T1 MRI contrast agents. T2 MRI is also possible due to the appreciable paramagnetic moments of Ln2O3 nanoparticles (Ln = Dy, Ho, and Tb) at room temperature arising from the nonzero orbital motion of 4f electrons. In addition, Ln2O3 nanoparticles are eligible as X-ray computed tomography contrast agents because of their high X-ray attenuation power. Since nanoparticle toxicity is of great concern, recent toxicity studies on Ln2O3 nanoparticles are also discussed.

scholarly journals Photoacoustic in vivo 3D imaging of tumor using a highly tumor-targeting probe under high-threshold conditions

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hisatsugu Yamada ◽  
Natsuki Matsumoto ◽  
Takanori Komaki ◽  
Hiroaki Konishi ◽  
Yu Kimura ◽  
...  
Keyword(s):  
Contrast Agents ◽  
Tumor Targeting ◽  
3D Imaging ◽  
Near Infrared ◽  
Three Dimensional ◽  
Cyanine Dye ◽  
High Threshold ◽  
Threshold Conditions

Abstract Three-dimensional (3D) representation of a tumor with respect to its size, shape, location, and boundaries is still a challenge in photoacoustic (PA) imaging using artificial contrast agents as probes. We carried out PA imaging of tumors in mice using 800RS-PMPC, which was obtained by coupling of 800RS, a near-infrared cyanine dye, with PMPC, a highly selective tumor-targeting methacrylate polymer having phosphorylcholine side chains, as a probe. The conjugate 800RS-PMPC forms compact nanoparticles (dDLS = 14.3 nm), retains the biocompatibility of the parent polymer (PMPC) and exhibits unprecedented PA performance. When applied to mice bearing a 6 × 3 × 3 mm3 tumor buried 6 mm beneath the skin, the probe 800RS-PMPC selectively accumulates in the tumor and emits PA signals that are strong enough to be unambiguously distinguished from noise signals of endogenous blood/hemoglobin. The PA image thus obtained under high-threshold conditions allows 3D characterization of the tumor in terms of its size, shape, location, and boundaries.

Tumor Environment-Responsive Degradable Branched Glycopolymer Magnetic Resonance Imaging Contrast Agent and Its Tumor-Targeted Imaging

2019 ◽  
Vol 15 (7) ◽  
pp. 1384-1400 ◽  
Author(s):  
Yang Wang ◽  
Yan Dai ◽  
Qiang Luo ◽  
Xiaoli Wei ◽  
Xueyang Xiao ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Contrast Agent ◽  
Contrast Agents ◽  
Signal Intensity ◽  
Tumor Targeting ◽  
Tumor Site ◽  
Resonance Imaging ◽  
Tumor Environment

Branched macromolecules have been used as carriers for imaging probes and drug delivery systems because of their tunable molecular structures, as well as their regular nanoscale structures and dimensions. We designed and synthesized two tumor environment-responsive branched and gadolinium (Gd)-based glycopolymer conjugates and investigated their potency as highly effective and safe magnetic resonance imaging (MRI) contrast agents. These branched macromolecules were prepared by one-pot reversible addition fragmentation chain transfer (RAFT) polymerization and conjugating chemistry. A biodegradable GFLG oligopeptide was used to successfully link the branch-chains of the branched macromolecules, finally a conjugate of this branched macromolecule and DOTA-Gd (HB-pGAEMA-Gd) with a molecular weight (MW) of 124 kDa was produced. Meanwhile, to improve the ability of tumor-targeting, we conjugated a tumor-targeting cRGDyK cyclic peptide to the branched molecule to prepare a tumor-targeted branched macromoleculeDOTA-Gd conjugate (HB-pGAEMA-RGD-Gd) with a MW of 136 kDa. The prepared branched macromolecules had a nanoscale hydrodynamic particle size and could be degraded into lower MW fragments with the cathepsin B. The aqueous phase relaxation efficiency of HB-pGAEMA-RGD-Gd (12.3 mM–1s–1 and HB-pGAEMA-Gd (13.2 mM–1s–1 was four times higher than that of DTPA-Gd (2.9 mM–1s–1), a clinically used contrast agent. In comparison with DTPA-Gd, the branched macromolecular contrast agents significantly enhanced the MRI signal intensity at the tumor site in vivo, and the enhancement of MRI signal intensity was up to 6 times that of the DTPA-Gd owing to their high relaxation efficiencies and accumulation at the tumor site. In addition, in vitro and in vivo toxicity studies indicated that the degradable macromolecular contrast agents had no significant toxicity.

scholarly journals Assessment of the Relaxation-Enhancing Properties of a Nitroxide-Based Contrast Agent TEEPO-Glc with In Vivo Magnetic Resonance Imaging

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Maiju Soikkeli ◽  
Mikko I. Kettunen ◽  
Riikka Nivajärvi ◽  
Venla Olsson ◽  
Seppo Rönkkö ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Contrast Agents ◽  
Tumor Targeting ◽  
Water Soluble ◽  
Organic Radicals ◽  
Resonance Imaging ◽  
Metal Free ◽  
Stable Nitroxide

Magnetic resonance imaging examinations are frequently carried out using contrast agents to improve the image quality. Practically all clinically used contrast agents are based on paramagnetic metals and lack in selectivity and specificity. A group of stable organic radicals, nitroxides, has raised interest as new metal-free contrast agents for MRI. Their structures can easily be modified to incorporate different functionalities. In the present study, a stable nitroxide TEEPO (2,2,6,6-tetraethylpiperidin-1-oxyl) was linked to a glucose moiety (Glc) to construct a water-soluble, potentially tumor-targeting compound with contrast-enhancing ability. The ability was assessed with in vivo MRI experiments. The constructed TEEPO-Glc agent proved to shorten the T1 relaxation time in tumor, while the T1 time in healthy brain tissue remained the same. The results indicate the potential of TEEPO-Glc as a valuable addition to the growing field of metal-free contrast enhancement in MRI-based diagnostics.

scholarly journals Improved pentamethine cyanine nanosensors for optoacoustic imaging of pancreatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew D. Laramie ◽  
Benjamin L. Fouts ◽  
William M. MacCuaig ◽  
Emmanuel Buabeng ◽  
Meredith A. Jones ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Contrast Agents ◽  
Optical Imaging ◽  
Silica Nanoparticles ◽  
Tumor Targeting ◽  
Tumor Imaging ◽  
Optoacoustic Imaging ◽  
Initial Development ◽  
Imaging Technology

AbstractOptoacoustic imaging is a new biomedical imaging technology with clear benefits over traditional optical imaging and ultrasound. While the imaging technology has improved since its initial development, the creation of dedicated contrast agents for optoacoustic imaging has been stagnant. Current exploration of contrast agents has been limited to standard commercial dyes that have already been established in optical imaging applications. While some of these compounds have demonstrated utility in optoacoustic imaging, they are far from optimal and there is a need for contrast agents with tailored optoacoustic properties. The synthesis, encapsulation within tumor targeting silica nanoparticles and applications in in vivo tumor imaging of optoacoustic contrast agents are reported.

Purification of the Antihemophilic Factor by Gel Filtration on Agarose

1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers
Keyword(s):  
Factor Viii ◽  
Plasma Proteins ◽  
Large Scale ◽  
Gel Filtration ◽  
Large Scale Preparation ◽  
Scale Preparation ◽  
Antihemophilic Factor

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.

Tantalum Oxide Nanoparticles as Versatile Contrast Agents for X-ray Computed Tomography

2020 ◽  
Author(s):  
Shatadru Chakravarty ◽  
Jeremy Hix ◽  
Kaitlyn Wieweora ◽  
Maximilian Volk ◽  
Elizabeth Kenyon ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Contrast Agents ◽  
Mesoporous Silica Nanoparticles ◽  
Sol Gel ◽  
Tantalum Oxide ◽  
High Signal ◽  
Drug Delivery Vehicles ◽  
X Ray Computed

Here we describe the synthesis, characterization and in vitro and in vivo performance of a series of tantalum oxide (TaOx) based nanoparticles (NPs) for computed tomography (CT). Five distinct versions of 9-12 nm diameter silane coated TaOx nanocrystals (NCs) were fabricated by a sol-gel method with varying degrees of hydrophilicity and with or without fluorescence, with the highest reported Ta content to date (78%). Highly hydrophilic NCs were left bare and were evaluated in vivo in mice for micro-CT of full body vasculature, where following intravenous injection, TaOx NCs demonstrate high CT contrast, circulation in blood for ~ 3 h, and eventual accumulation in RES organs; and following injection locally in the mammary gland, where the full ductal tree structure can be clearly delineated. Partially hydrophilic NCs were encapsulated within mesoporous silica nanoparticles (MSNPs; TaOx@MSNPs) and hydrophobic NCs were encapsulated within poly(lactic-co-glycolic acid) (PLGA; TaOx@PLGA) NPs, serving as potential CT-imagable drug delivery vehicles. Bolus intramuscular injections of TaOx@PLGA NPs and TaOx@MSNPs to mimic the accumulation of NPs at a tumor site produce high signal enhancement in mice. In vitro studies on bare NCs and formuated NPs demonstrate high cytocompatibility and low dissolution of TaOx. This work solidifies that TaOx-based NPs are versatile contrast agents for CT.

Rapid Catalyst Capture Enables Metal-Free Parahydrogen-Based Hyperpolarized Contrast Agents

2018 ◽  
Author(s):  
Danila Barskiy ◽  
Lucia Ke ◽  
Xingyang Li ◽  
Vincent Stevenson ◽  
Nevin Widarman ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Contrast Agents ◽  
Inductively Coupled Plasma ◽  
Organometallic Compounds ◽  
Atomic Emission ◽  
Platinum Group Metals ◽  
Resonance Spectroscopy ◽  
Plasma Atomic Emission ◽  
Inductively Coupled

<p>Hyperpolarization techniques based on the use of parahydrogen provide orders of magnitude signal enhancement for magnetic resonance spectroscopy and imaging. The main drawback limiting widespread applicability of parahydrogen-based techniques in biomedicine is the presence of organometallic compounds (the polarization transfer catalysts) in solution with hyperpolarized contrast agents. These catalysts are typically complexes of platinum-group metals and their administration in vivo should be avoided.</p> <p><br></p><p>Herein, we show how extraction of a hyperpolarized compound from an organic phase to an aqueous phase combined with a rapid (less than 10 seconds) Ir-based catalyst capture by metal scavenging agents can produce pure parahydrogen-based hyperpolarized contrast agents as demonstrated by high-resolution nuclear magnetic resonance (NMR) spectroscopy and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The presented methodology enables fast and efficient means of producing pure hyperpolarized aqueous solutions for biomedical and other uses.</p>

Rapid Catalyst Capture Enables Metal-Free Parahydrogen-Based Hyperpolarized Contrast Agents

2018 ◽  
Author(s):  
Danila Barskiy ◽  
Lucia Ke ◽  
Xingyang Li ◽  
Vincent Stevenson ◽  
Nevin Widarman ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Contrast Agents ◽  
Inductively Coupled Plasma ◽  
Organometallic Compounds ◽  
Atomic Emission ◽  
Platinum Group Metals ◽  
Resonance Spectroscopy ◽  
Plasma Atomic Emission ◽  
Inductively Coupled

<p>Hyperpolarization techniques based on the use of parahydrogen provide orders of magnitude signal enhancement for magnetic resonance spectroscopy and imaging. The main drawback limiting widespread applicability of parahydrogen-based techniques in biomedicine is the presence of organometallic compounds (the polarization transfer catalysts) in solution with hyperpolarized contrast agents. These catalysts are typically complexes of platinum-group metals and their administration in vivo should be avoided.</p> <p><br></p><p>Herein, we show how extraction of a hyperpolarized compound from an organic phase to an aqueous phase combined with a rapid (less than 10 seconds) Ir-based catalyst capture by metal scavenging agents can produce pure parahydrogen-based hyperpolarized contrast agents as demonstrated by high-resolution nuclear magnetic resonance (NMR) spectroscopy and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The presented methodology enables fast and efficient means of producing pure hyperpolarized aqueous solutions for biomedical and other uses.</p>

Supramolecular Enhancement of Aminoxyl ORCA Contrast Agents

2019 ◽  
Author(s):  
Hamilton Lee ◽  
Jenica Lumata ◽  
Michael A. Luzuriaga ◽  
Candace Benjamin ◽  
Olivia Brohlin ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Side Effects ◽  
Magnetic Resonance ◽  
Tobacco Mosaic Virus ◽  
Contrast Agents ◽  
Single Molecule ◽  
Organic Radical ◽  
Resonance Imaging ◽  
Physiological Conditions

<div><div><div><p>Many contrast agents for magnetic resonance imaging are based on gadolinium, however side effects limit their use in some patients. Organic radical contrast agents (ORCAs) are potential alternatives, but are reduced rapidly in physiological conditions and have low relaxivities as single molecule contrast agents. Herein, we use a supramolecular strategy where cucurbit[8]uril binds with nanomolar affinities to ORCAs and protects them against biological reductants to create a stable radical in vivo. We further over came the weak contrast by conjugating this complex on the surface of a self-assembled biomacromolecule derived from the tobacco mosaic virus.</p></div></div></div>

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