Porphyrin-based photosensitizers and the corresponding multifunctional nanoplatforms for cancer-imaging and phototherapy

2015 ◽  
Vol 19 (01-03) ◽  
pp. 109-134 ◽  
Author(s):  
Avinash Srivatsan ◽  
Joseph R. Missert ◽  
Santosh K. Upadhyay ◽  
Ravindra K. Pandey
Keyword(s):  
Tumor Imaging ◽  
Cancer Imaging ◽  
Nuclear Imaging ◽  
Review Article ◽  
Whole Body ◽  
Tumor Uptake ◽  
Light Dosimetry ◽  
Gold Nanocages

This review article briefly describes: (a) the advantages in developing multifunctional nanoparticles for cancer-imaging and therapy, (b) the advantages and limitations of most of the porphyrin-based compounds in fluorescence imaging and photodynamic therapy (PDT), (c) problems associated with current Food and Drug Administration (FDA) approved photosensitizers, (d) challenges in developing in vivo target-specific PDT agents, (e) development of porphyrin-based nuclear-imaging agents (PET, SPECT) with an option of PDT, (f) the importance of light dosimetry in PDT, (g) the role of whole body or local hyperthermia in enhancing tumor-uptake, tumor-imaging and phototherapy and finally, (h) the advantages of photosensitizer-gold nanocages (Ps- Au NC) in photoacoustic and PDT.

scholarly journals Role of antennary structure of N-linked sugar chains in renal handling of recombinant human erythropoietin

Blood ◽  
1995 ◽  
Vol 86 (11) ◽  
pp. 4097-4104 ◽  
Author(s):  
T Misaizu ◽  
S Matsuki ◽  
TW Strickland ◽  
M Takeuchi ◽  
A Kobata ◽  
...  
Keyword(s):  
Whole Body ◽  
Renal Handling ◽  
Sugar Chain ◽  
Erythroid Progenitor ◽  
Human Erythropoietin ◽  
Sugar Chains ◽  
Effective Transfer ◽  
Branched Structure

To elucidate the role of the branched structure of sugar chains of human erythropoietin (EPO) in the expression of in vivo activity, the pharmacokinetic profile of a less active recombinant human EPO sample (EPO-bi) enriched with biantennary sugar chains was compared with that of a highly active control EPO sample enriched with tetraantennary sugar chains. After an intravenous injection in rats, 125I-EPO-bi disappeared from the plasma with 3.2 times greater total body clearance (Cltot) than control 125I-EPO. Whole-body autoradiography after 20 minutes of administration indicated that the overall distribution of radioactivity is similar, but 125I-EPO-bi showed a higher level of radioactivity in the kidneys than control 125I-EPO. Quantitative determination of radioactivity in the tissues also indicated that radioactivity of 125I-EPO-bi in the kidneys was two times higher than that of control 125I-EPO. The difference in plasma disappearance between 125I-EPO-bi and control 125I-EPO was not observed in bilaterally nephrectomized rats. The distribution of 125I-EPO-bi to bone marrow and spleen was similarly inhibited by simultaneous injection of excess amounts of either the nonlabeled EPO-bi or control EPO. These results indicate that the low in vivo biologic activity of EPO-bi results from rapid clearance from the systemic circulation by renal handling. Thus, the well-branched structure of the N-linked sugar chain of EPO is suggested to play an important role in maintaining its higher plasma level, which guarantees an effective transfer to target organs and stimulation of erythroid progenitor cells.

scholarly journals Radioanalytical Techniques to Quantitatively Assess the Biological Uptake and In Vivo Behavior of Hazardous Substances

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3985
Author(s):  
Jae Young Lee ◽  
Sajid Mushtaq ◽  
Jung Eun Park ◽  
Hee Soon Shin ◽  
So-Young Lee ◽  
...  
Keyword(s):  
Nuclear Imaging ◽  
Hazardous Substances ◽  
Environmental Research ◽  
Whole Body ◽  
Whole Body Imaging ◽  
Toxic Substances ◽  
Industrial Chemicals ◽  
Biological Uptake ◽  
Radioanalytical Methods

Concern about environmental exposure to hazardous substances has grown over the past several decades, because these substances have adverse effects on human health. Methods used to monitor the biological uptake of hazardous substances and their spatiotemporal behavior in vivo must be accurate and reliable. Recent advances in radiolabeling chemistry and radioanalytical methodologies have facilitated the quantitative analysis of toxic substances, and whole-body imaging can be achieved using nuclear imaging instruments. Herein, we review recent literature on the radioanalytical methods used to study the biological distribution, changes in the uptake and accumulation of hazardous substances, including industrial chemicals, nanomaterials, and microorganisms. We begin with an overview of the radioisotopes used to prepare radiotracers for in vivo experiments. We then summarize the results of molecular imaging studies involving radiolabeled toxins and their quantitative assessment. We conclude the review with perspectives on the use of radioanalytical methods for future environmental research.

Studies of the antibody-dependent killing of schistosomula of Schistosoma mansoni employing haptenic target antigens. Analysis of mechanisms responsible for the rejection of parasites in vivo

Parasitology ◽  
1981 ◽  
Vol 83 (3) ◽  
pp. 543-558
Author(s):  
Gina Moser ◽  
F. von Lichtenberg ◽  
A. Sher
Keyword(s):  
Schistosoma Mansoni ◽  
Passive Immunization ◽  
Early Response ◽  
Challenge Infection ◽  
Delayed Hypersensitivity ◽  
Whole Body ◽  
Hypersensitivity Response ◽  
Time Points

SUMMARYSchistosomula, surface labelled with trinitrophenyl (TNP) target antigens were tested for their susceptibility to killing by humoral- or cell-mediated anti-TNP effector mechanisms in vivo. It was found that mice passively immunized with anti-TNP serum effectively rejected an intravenous (i.v.) challenge infection with TNP-labelled schistosomula. In contrast, mice which demonstrated a strong TNP-specific, delayed hypersensitivity response to the haptenated larvae as evidenced by ear swelling, were unable to eliminate the same challenge infection. Significant passive immunization against TNP-labelled schistosomula was shown to require microlitre quantities of anti-TNP serum and could be conferred with an IgG fraction purified from the serum. The role of cells in the antibody-dependent rejection of TNP-labelled schistosomula was investigated using histopathological methods. In passively immunized mice, haptenated larvae elicited neutrophil-enriched focal reactions in the lungs and showed evidence of degeneration as early as 2 h after injection. These cellular reactions were not observed in recipients which had received prior whole-body irradiation. Nevertheless, by 24 h TNP-labelled larvae were found to have been killed in the lungs of the irradiated mice despite the absence of significant cellular attack. The above observations suggest that the antibody-dependent destruction of haptenated schistosomula results from two overlapping responses, an early response mediated by radio-sensitive cells and a second, radio-resistant response manifesting its effects at later time points. Since mice genetically deficient in the fifth component of complement fail to develop the later response, it probably reflects the effect of the lytic pathway of complement on the parasite.

scholarly journals Key-Protease Inhibition Regimens Promote Tumor Targeting of Neurotensin Radioligands

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 528
Author(s):  
Panagiotis Kanellopoulos ◽  
Aikaterini Kaloudi ◽  
Marion de Jong ◽  
Eric P. Krenning ◽  
Berthold A. Nock ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Ace Inhibitor ◽  
Tumor Imaging ◽  
Colon Adenocarcinoma ◽  
Ace Inhibition ◽  
Tumor Uptake ◽  
Protease Inhibition ◽  
Structural Modifications

Neurotensin subtype 1 receptors (NTS1R) represent attractive molecular targets for directing radiolabeled neurotensin (NT) analogs to tumor lesions for diagnostic and therapeutic purposes. This approach has been largely undermined by the rapid in vivo degradation of linear NT-based radioligands. Herein, we aim to increase the tumor targeting of three 99mTc-labeled NT analogs by the in-situ inhibition of two key proteases involved in their catabolism. DT1 ([N4-Gly7]NT(7-13)), DT5 ([N4-βAla7,Dab9]NT(7-13)), and DT6 ([N4-βAla7,Dab9,Tle12]]NT(7-13)) were labeled with 99mTc. Their profiles were investigated in NTS1R-positive colon adenocarcinoma WiDr cells and mice treated or not with the neprilysin (NEP)-inhibitor phosphoramidon (PA) and/or the angiotensin converting enzyme (ACE)-inhibitor lisinopril (Lis). Structural modifications led to the partial stabilization of 99mTc-DT6 in peripheral mice blood (55.1 ± 3.9% intact), whereas 99mTc-DT1 and 99mTc-DT5 were totally degraded within 5 min. Coinjection of PA and/or Lis significantly stabilized all three analogs, leading to a remarkable enhancement of tumor uptake for 99mTc-DT1 and 99mTc-DT5, but was less effective in the case of poorly internalizing 99mTc-DT6. In conclusion, NEP and/or ACE inhibition represents a powerful tool to improve tumor targeting and the overall pharmacokinetics of NT-based radioligands, and warrants further validation in the field of NTS1R-targeted tumor imaging and therapy.

scholarly journals Ablation of 3-Phosphoinositide-Dependent Protein Kinase 1 (PDK1) in Vascular Endothelial Cells Enhances Insulin Sensitivity by Reducing Visceral Fat and Suppressing Angiogenesis

2012 ◽  
Vol 26 (1) ◽  
pp. 95-109 ◽  
Author(s):  
Kazuhito Tawaramoto ◽  
Ko Kotani ◽  
Mitsuru Hashiramoto ◽  
Yukiko Kanda ◽  
Tomoki Nagare ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Insulin Sensitivity ◽  
Protein Kinase ◽  
Vascular Endothelial Cells ◽  
Whole Body ◽  
Vascular Endothelial ◽  
Dependent Protein Kinase ◽  
Dependent Protein

Abstract The phosphatidylinositol 3-kinase signaling pathway in vascular endothelial cells is important for systemic angiogenesis and glucose metabolism. In this study, we addressed the precise role of the 3-phosphoinositide-dependent protein kinase 1 (PDK1)-regulated signaling network in endothelial cells in vivo, using vascular endothelial PDK1 knockout (VEPDK1KO) mice. Surprisingly, VEPDK1KO mice manifested enhanced glucose tolerance and whole-body insulin sensitivity due to suppression of their hepatic glucose production with no change in either peripheral glucose disposal or even impaired vascular endothelial function at 6 months of age. When mice were fed a standard diet at 6 months of age and a high-fat diet at 3 months of age, hypertrophy of epididymal adipose tissues was inhibited, adiponectin mRNA was significantly increased, and mRNA of MCP1, leptin, and TNFα was decreased in the white adipose tissue of VEPDK1KO mice in comparison with controls. Consequently, both the circulating adiponectin levels and the activity of hepatic AMP-activated protein kinase were significantly increased, subsequently enhancing whole-body insulin sensitivity and energy expenditure with increased hepatic fatty acid oxidation in VEPDK1KO mice. These results provide the first in vivo evidence that lowered angiogenesis through the deletion of PDK1 signaling not only interferes with the growth of adipose tissue but also induces increased energy expenditure due to amelioration of the adipocytokine profile. This demonstrates an unexpected role of PDK1 signaling in endothelial cells on the maintenance of proper glucose homeostasis through the regulation of adipocyte development.

scholarly journals Mesenchymal Igf2 is a major paracrine regulator of pancreatic growth and function

2019 ◽  
Author(s):  
Constanze M. Hammerle ◽  
Ionel Sandovici ◽  
Gemma V. Brierley ◽  
Nicola M. Smith ◽  
Warren E. Zimmer ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Whole Body ◽  
Imprinted Genes ◽  
Paracrine Signalling ◽  
Genetic Mechanisms ◽  
Pancreatic Epithelium ◽  
And Function ◽  
Maternal Glucose

AbstractThe genetic mechanisms that determine the size of the adult pancreas are poorly understood. Here we demonstrate that many imprinted genes are highly expressed in the pancreatic mesenchyme, and explore the role of Igf2 in-vivo. Mesenchyme-specific Igf2 deletion results in acinar and beta-cell hypoplasia, postnatal whole-body growth restriction and maternal glucose intolerance during pregnancy. Surprisingly, mesenchymal mass is unaffected, suggesting that the mesenchyme is a developmental reservoir of IGF2 used for paracrine signalling. The unique actions of mesenchymal IGF2 are demonstrated by the absence of phenotypes upon Igf2 deletion in the developing pancreatic epithelium. Furthermore, increased IGF2 activity specifically in the mesenchyme, through Igf2 loss-of-imprinting or Igf2r deletion, leads to pancreatic acinar overgrowth. Ex-vivo exposure of primary acinar cells to exogenous IGF2 increases cell proliferation and amylase production through AKT signalling. We propose that mesenchymal Igf2, and perhaps other imprinted genes, are key developmental regulators of adult pancreas size and function.

BODY ORGAN CYTOCHROME OXIDASE ACTIVITY IN COLD- AND WARM-ACCLIMATED RATS

1963 ◽  
Vol 41 (9) ◽  
pp. 1847-1854 ◽  
Author(s):  
Ladislav Janský
Keyword(s):  
Steady State ◽  
Cytochrome Oxidase ◽  
Oxidase Activity ◽  
Whole Body ◽  
Cytochrome Oxidase Activity ◽  
Full Capacity ◽  
Body Organ ◽  
Total Body

The cytochrome oxidase activity was estimated in homogenates of the whole body and in nine body organs of cold- and warm-acclimated rats. The total body cytochrome oxidase activity expressed in terms of oxygen consumption was similar in cold- and warm-acclimated rats. In cold-acclimated animals the total cytochrome oxidase activity did not differ from maximal steady state metabolism measured in vivo, while in warm-acclimated rats the total cytochrome oxidase activity was almost twice as great as the maximal steady state metabolism. The results indicate that warm-acclimated rats do not utilize the full capacity of the cytochrome system and that cold-acclimation makes full exploitation of the oxidase capacity possible. In cold-acclimated rats the cytochrome oxidase activity of the muscles comprised 57% of the total, the liver 22.5%, and the skin 6%, with smaller roles for other organs. The role of the liver was greater in cold-acclimated than in warm-acclimated rats.

Cytoarchitecture of the Xenopus thymus following gamma-irradiation

Development ◽  
1987 ◽  
Vol 100 (1) ◽  
pp. 95-105
Author(s):  
JH Russ ◽  
JD Horton
Keyword(s):  
Gamma Irradiation ◽  
Tolerance Induction ◽  
Cell Types ◽  
Whole Body ◽  
Thymic Stromal Cells ◽  
Normal Architecture

This paper describes in vitro and in vivo attempts to deplete the 4- to 8-month-old Xenopus laevis (J strain) thymus of its lymphocyte compartment. Gamma irradiation (2-3000 rad) of the excised thymus, followed by two weeks in organ culture, is effective in removing lymphocytes, but causes drastic reduction in size and loss of normal architecture. In contrast, in vivo whole-body irradiation (3000 rad) and subsequent in situ residence for 8-14 days proves successful in providing a lymphocyte-depleted froglet thymus without loss of cortical and medullary zones. In vivo-irradiated thymuses are about half normal size, lack cortical lymphocytes, but still retain some medullary thymocytes; they show no signs of lymphocyte regeneration when subsequently organ cultured for 2 weeks. Light microscopy of 1 micron, plastic-embedded sections and electron microscopy reveal that a range of thymic stromal cell types are retained and that increased numbers of cysts, mucous and myoid cells are found in the thymus following whole-body irradiation. In vivo-irradiated thymuses are therefore suitable for implantation studies exploring the role of thymic stromal cells in tolerance induction of differentiating T lymphocytes.

Measuring whole-body actin/myosin protein breakdown in mice using a primed constant stable isotope-infusion protocol

2003 ◽  
Vol 104 (6) ◽  
pp. 585-590 ◽  
Author(s):  
Yvonne L. J. VISSERS ◽  
Maarten F. VON MEYENFELDT ◽  
Valeria B. BRAULIO ◽  
Yvette C. LUIKING ◽  
Nicolaas E. P. DEUTZ
Keyword(s):  
Stable Isotope ◽  
Total Protein ◽  
Myofibrillar Protein ◽  
Whole Body ◽  
Constant Infusion ◽  
Protein Breakdown ◽  
Net Protein ◽  
Infusion Protocol

To measure actin/myosin protein breakdown, the 24 h excretion of Nτ-methylhistidine (3MH) is used. However, in mice, this method is invalid. Therefore we have developed a liquid chromatography-MS technique to measure the tracer/tracee ratio and concentration of 3MH in plasma, enabling an in vivo primed constant infusion protocol with a deuterated stable isotope of 3MH. We tested this model by giving a primed constant infusion of L-[3-methyl-2H3]histidine, L-[phenyl-2H5]phenylalanine and L-[phenyl-2H2]tyrosine to three anaesthetized experimental groups: mice receiving saline intraperitoneally (i.p.) (CON), mice receiving saline i.p. and starved for 9 h (STA), and mice receiving lipopolysaccharide i.p. and starved for 9 h (STA + LPS). The contribution of myofibrillar to total protein breakdown was significantly lower in the STA group than the CON group (30±4% and 54±14% respectively; P<0.05), and was significantly higher in the STA + LPS group than the STA group (52±7% and 30±4% respectively; P<0.05). Whole-body myofibrillar protein breakdown, total protein breakdown, protein synthesis and net protein breakdown were not different between the groups. We conclude that this in vivo primed constant stable isotope-infusion protocol can give valuable information about the role of actin/myosin protein breakdown in mice.

Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements

2014 ◽  
Vol 306 (12) ◽  
pp. E1367-E1377 ◽  
Author(s):  
Thomas V. Lakeland ◽  
Melissa L. Borg ◽  
Maria Matzaris ◽  
Amany Abdelkader ◽  
Roger G. Evans ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Body Mass ◽  
Pigment Epithelium ◽  
In Vivo Studies ◽  
Whole Body ◽  
Pigment Epithelium Derived Factor ◽  
Metabolic Role

Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo.

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