scholarly journals Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors

2018 ◽  
Vol 115 (12) ◽  
pp. E2811-E2818 ◽  
Author(s):  
Linden C. Wyatt ◽  
Anna Moshnikova ◽  
Troy Crawford ◽  
Donald M. Engelman ◽  
Oleg A. Andreev ◽  
...  
Keyword(s):  
Circular Dichroism ◽  
Targeted Delivery ◽  
Tumor Imaging ◽  
Intracellular Delivery ◽  
Membrane Lipid ◽  
Wide Range ◽  
Ph Dependent ◽  
Circular Dichroïsm

The pH (low) insertion peptides (pHLIPs) target acidity at the surfaces of cancer cells and show utility in a wide range of applications, including tumor imaging and intracellular delivery of therapeutic agents. Here we report pHLIP constructs that significantly improve the targeted delivery of agents into tumor cells. The investigated constructs include pHLIP bundles (conjugates consisting of two or four pHLIP peptides linked by polyethylene glycol) and Var3 pHLIPs containing either the nonstandard amino acid, γ-carboxyglutamic acid, or a glycine−leucine−leucine motif. The performance of the constructs in vitro and in vivo was compared with previous pHLIP variants. A wide range of experiments was performed on nine constructs including (i) biophysical measurements using steady-state and kinetic fluorescence, circular dichroism, and oriented circular dichroism to study the pH-dependent insertion of pHLIP variants across the membrane lipid bilayer; (ii) cell viability assays to gauge the pH-dependent potency of peptide-toxin constructs by assessing the intracellular delivery of the polar, cell-impermeable cargo molecule amanitin at physiological and low pH (pH 7.4 and 6.0, respectively); and (iii) tumor targeting and biodistribution measurements using fluorophore-peptide conjugates in a breast cancer mouse model. The main principles of the design of pHLIP variants for a range of medical applications are discussed.

Multifunctional graphene oxide for bioimaging: emphasis on biological research

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Do Won Hwang ◽  
Byung Hee Hong ◽  
Dong Soo Lee
Keyword(s):  
Graphene Oxide ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Biological Research ◽  
Natural Interaction ◽  
Drug Delivery Carrier ◽  
Wide Range ◽  
Surface Enhanced Raman

AbstractGraphene oxide (GO) nanomaterials offer a wide range of bioimaging applicability. Almost complete quenching ability of fluorescence by GO and natural interaction of GO with single stranded nucleic acid made GO a useful and intriguing multifunctional nanoplatform both as a biosensor for in vitro microplate diagnostics and as a drug delivery carrier for targeted delivery. GO’s large surface area and strong near infrared absorbance contribute to enhancement of a therapeutic effect with abundant loading of drugs for possible photothermal and photodynamic therapy. Bioimaging capability of GO made it a good theranostic tool, while enabling tracing in vivo pharmacokinetics during concurrent treatment. Fluorescence, either signal on or off, Raman and surface-enhanced Raman scattering (SERs), photoacoustic, and radionuclide imaging modalities can be used for theranostic purposes using GO nanomaterials. In this review, we highlight current applications of GO for bioimaging that are classified into in vitro microplate, in vitro cellular and in vivo bioimaging.

A Circular Dichroism and Photoacoustic Dual-Mode Probe for Detection In Vitro and Imaging In Vivo of Hydroxyl Radicals

2022 ◽  
Author(s):  
Shulong Wang ◽  
Liangliang Zhang ◽  
Yanni Luo ◽  
Yulong Bai ◽  
Yong Huang ◽  
...  
Keyword(s):  
Circular Dichroism ◽  
Hydroxyl Radicals ◽  
Dual Mode ◽  
Circular Dichroïsm

Phytochemical and Bioactive Potential of in vivo and in vitro Grown Plants of Centaurea ragusina L. - Detection of DNA/RNA Active Compounds in Plant Extracts via Thermal Denaturation and Circular Dichroism

2017 ◽  
Vol 28 (6) ◽  
pp. 584-592 ◽  
Author(s):  
Valerija Vujčić ◽  
Sandra Radić Brkanac ◽  
Ivana Radojčić Redovniković ◽  
Siniša Ivanković ◽  
Ranko Stojković ◽  
...  
Keyword(s):  
Circular Dichroism ◽  
Plant Extracts ◽  
Thermal Denaturation ◽  
Active Compounds ◽  
Bioactive Potential ◽  
Circular Dichroïsm

Patients with fever of unknown origin (FUO): diagnosis by nuclear medicine imaging

2001 ◽  
Vol 40 (03) ◽  
pp. 59-70 ◽  
Author(s):  
W. Becker ◽  
J. Meiler
Keyword(s):  
Nuclear Medicine ◽  
Fever Of Unknown Origin ◽  
Tumor Imaging ◽  
White Blood Cells ◽  
Unknown Origin ◽  
Final Diagnosis ◽  
Recurrent Fever ◽  
Nuclear Medicine Imaging

SummaryFever of unknown origin (FUO) in immunocompetent and non neutropenic patients is defined as recurrent fever of 38,3° C or greater, lasting 2-3 weeks or longer, and undiagnosed after 1 week of appropriate evaluation. The underlying diseases of FUO are numerous and infection accounts for only 20-40% of them. The majority of FUO-patients have autoimmunity and collagen vascular disease and neoplasm, which are responsible for about 50-60% of all cases. In this respect FOU in its classical definition is clearly separated from postoperative and neutropenic fever where inflammation and infection are more common. Although methods that use in-vitro or in-vivo labeled white blood cells (WBCs) have a high diagnostic accuracy in the detection and exclusion of granulocytic pathology, they are only of limited value in FUO-patients in establishing the final diagnosis due to the low prevalence of purulent processes in this collective. WBCs are more suited in evaluation of the focus in occult sepsis. Ga-67 citrate is the only commercially available gamma emitter which images acute, chronic, granulomatous and autoimmune inflammation and also various malignant diseases. Therefore Ga-67 citrate is currently considered to be the tracer of choice in the diagnostic work-up of FUO. The number of Ga-67-scans contributing to the final diagnosis was found to be higher outside Germany than it has been reported for labeled WBCs. F-l 8-2’-deoxy-2-fluoro-D-glucose (FDG) has been used extensively for tumor imaging with PET. Inflammatory processes accumulate the tracer by similar mechanisms. First results of FDG imaging demonstrated, that FDG may be superior to other nuclear medicine imaging modalities which may be explained by the preferable tracer kinetics of the small F-l 8-FDG molecule and by a better spatial resolution of coincidence imaging in comparison to a conventional gamma camera.

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

Spectroscopic Studies of Asparaginyl-tRNA Synthetase from Entamoeba histolytica

2019 ◽  
Vol 26 (6) ◽  
pp. 435-448
Author(s):  
Priyanka Biswas ◽  
Dillip K. Sahu ◽  
Kalyanasis Sahu ◽  
Rajat Banerjee
Keyword(s):  
Circular Dichroism ◽  
Steady State ◽  
Entamoeba Histolytica ◽  
Protein Concentration ◽  
Trna Synthetase ◽  
Solvent Exposure ◽  
Steady State Fluorescence ◽  
State Process ◽  
Wide Range ◽  
Circular Dichroïsm

Background: Aminoacyl-tRNA synthetases play an important role in catalyzing the first step in protein synthesis by attaching the appropriate amino acid to its cognate tRNA which then transported to the growing polypeptide chain. Asparaginyl-tRNA Synthetase (AsnRS) from Brugia malayi, Leishmania major, Thermus thermophilus, Trypanosoma brucei have been shown to play an important role in survival and pathogenesis. Entamoeba histolytica (Ehis) is an anaerobic eukaryotic pathogen that infects the large intestines of humans. It is a major cause of dysentery and has the potential to cause life-threatening abscesses in the liver and other organs making it the second leading cause of parasitic death after malaria. Ehis-AsnRS has not been studied in detail, except the crystal structure determined at 3 Å resolution showing that it is primarily α-helical and dimeric. It is a homodimer, with each 52 kDa monomer consisting of 451 amino acids. It has a relatively short N-terminal as compared to its human and yeast counterparts. Objective: Our study focusses to understand certain structural characteristics of Ehis-AsnRS using biophysical tools to decipher the thermodynamics of unfolding and its binding properties. Methods: Ehis-AsnRS was cloned and expressed in E. coli BL21DE3 cells. Protein purification was performed using Ni-NTA affinity chromatography, following which the protein was used for biophysical studies. Various techniques such as steady-state fluorescence, quenching, circular dichroism, differential scanning fluorimetry, isothermal calorimetry and fluorescence lifetime studies were employed for the conformational characterization of Ehis-AsnRS. Protein concentration for far-UV and near-UV circular dichroism experiments was 8 µM and 20 µM respectively, while 4 µM protein was used for the rest of the experiments. Results: The present study revealed that Ehis-AsnRS undergoes unfolding when subjected to increasing concentration of GdnHCl and the process is reversible. With increasing temperature, it retains its structural compactness up to 45ºC before it unfolds. Steady-state fluorescence, circular dichroism and hydrophobic dye binding experiments cumulatively suggest that Ehis-AsnRS undergoes a two-state transition during unfolding. Shifting of the transition mid-point with increasing protein concentration further illustrate that dissociation and unfolding processes are coupled indicating the absence of any detectable folded monomer. Conclusion: This article indicates that GdnHCl induced denaturation of Ehis-AsnRS is a two – state process and does not involve any intermediate; unfolding occurs directly from native dimer to unfolded monomer. The solvent exposure of the tryptophan residues is biphasic, indicating selective quenching. Ehis-AsnRS also exhibits a structural as well as functional stability over a wide range of pH.

Internal and External Triggering Mechanism of “Smart” Nanoparticle-Based DDSs in Targeted Tumor Therapy

2018 ◽  
Vol 24 (15) ◽  
pp. 1639-1651 ◽  
Author(s):  
Xian-ling Qian ◽  
Jun Li ◽  
Ran Wei ◽  
Hui Lin ◽  
Li-xia Xiong
Keyword(s):  
Targeted Delivery ◽  
Tumor Therapy ◽  
Burst Release ◽  
Tumor Site ◽  
Chemotherapeutic Drugs ◽  
Triggering Mechanism ◽  
Triggering Factors ◽  
Or Genes

Background: Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: “passive”, “active”, and “smart” targeting. Objective: To summarize the mechanisms of various internal and external “smart” stimulating factors on the basis of findings from in vivo and in vitro studies. Method: A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Results: Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), “smart” DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. Conclusion: In this review article, we summarize and classify the internal and external triggering mechanism of “smart” nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding.

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