scholarly journals Harnessing subcellular-resolved organ distribution of cationic copolymer-functionalized fluorescent nanodiamonds for optimal delivery of active siRNA to a xenografted tumor in mice

Nanoscale ◽  
2021 ◽  
Author(s):  
Sandra Claveau ◽  
Marek Kindermann ◽  
Alexandre Papine ◽  
Zamira Vanessa Diaz-Riascos ◽  
Xavier Délen ◽  
...  

Diamond nanoparticles (nanodiamonds) can transport active drugs in cultured cells as well as in vivo. However, in the latter case, methods allowing to determine their bioavailability accurately are still lacking....

Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.


Author(s):  
Frederick A. Murphy ◽  
Alyne K. Harrison ◽  
Sylvia G. Whitfield

The bullet-shaped viruses are currently classified together on the basis of similarities in virion morphology and physical properties. Biologically and ecologically the member viruses are extremely diverse. In searching for further bases for making comparisons of these agents, the nature of host cell infection, both in vivo and in cultured cells, has been explored by thin-section electron microscopy.


Author(s):  
N.K.R. Smith ◽  
K.E. Hunter ◽  
P. Mobley ◽  
L.P. Felpel

Electron probe energy dispersive x-ray microanalysis (XRMA) offers a powerful tool for the determination of intracellular elemental content of biological tissue. However, preparation of the tissue specimen , particularly excitable central nervous system (CNS) tissue , for XRMA is rather difficult, as dissection of a sample from the intact organism frequently results in artefacts in elemental distribution. To circumvent the problems inherent in the in vivo preparation, we turned to an in vitro preparation of astrocytes grown in tissue culture. However, preparations of in vitro samples offer a new and unique set of problems. Generally, cultured cells, growing in monolayer, must be harvested by either mechanical or enzymatic procedures, resulting in variable degrees of damage to the cells and compromised intracel1ular elemental distribution. The ultimate objective is to process and analyze unperturbed cells. With the objective of sparing others from some of the same efforts, we are reporting the considerable difficulties we have encountered in attempting to prepare astrocytes for XRMA.Tissue cultures of astrocytes from newborn C57 mice or Sprague Dawley rats were prepared and cultured by standard techniques, usually in T25 flasks, except as noted differently on Cytodex beads or on gelatin. After different preparative procedures, all samples were frozen on brass pins in liquid propane, stored in liquid nitrogen, cryosectioned (0.1 μm), freeze dried, and microanalyzed as previously reported.


1981 ◽  
Vol 20 (02) ◽  
pp. 90-93
Author(s):  
P.B. Parab ◽  
U.R. Raikar ◽  
R.D. Ganatra ◽  
M. C. Patel

Phenolphthalexon, a compound with iminodiacetic acid as a functional group, has been labelled with 113mIn to high chemical purity and its usefulness in studies of biliary excretion patency has been studied. Organ distribution of 113mIn-phenolphthalexon in mice was characterized by high liver uptake (50.8% of the administered dose after 5 min) and rapid clearance through the gall bladder. An animal model for studying obstruction of biliary excretion has been developed. Data on the kinetics of the radiopharmaceutical were obtained by collecting in-vivo data through an on-line computer.


1981 ◽  
Vol 46 (03) ◽  
pp. 658-661 ◽  
Author(s):  
C Korninger ◽  
J M Stassen ◽  
D Collen

SummaryThe turnover of highly purified human extrinsic plasminogen activator (EPA) (one- and two-chain form) was studied in rabbits. Following intravenous injection, EPA-activity declined rapidly. The disappearance rate of EPA from the plasma could adequately be described by a single exponential term with a t ½ of approximately 2 min for both the one-chain and two-chain forms of EPA.The clearance and organ distribution of EPA was studied by using 125I-labeled preparations. Following intravenous injection of 125I-1abeled EPA the radioactivity disappeared rapidly from the plasma also with a t ½ of approximately 2 min down to a level of 15 to 20 percent, followed by a small rise of blood radioactivity. Gel filtration of serial samples revealed that the secondary increase of the radioactivity was due to the reappearance of radioactive breakdown products in the blood. Measurement of the organ distribution of 125I at different time intervals revealed that EPA was rapidly accumulated in the liver, followed by a release of degradation products in the blood.Experimental hepatectomy markedly prolonged the half-life of EPA in the blood. Blocking the active site histidine of EPA had no effect on the half-life of EPA in blood nor on the gel filtration patterns of 125I in serial plasma samples.It is concluded that human EPA is rapidly removed from the blood of rabbits by clearance and degradation in the liver. Recognition by the liver does not require a functional active site in the enzyme. Neutralization in plasma by protease inhibitors does not represent a significant pathway of EPA inactivation in vivo.


2020 ◽  
Vol 10 ◽  
Author(s):  
Aditya Nath Pandey ◽  
Kuldeep Rajpoot ◽  
Sunil K. Jain

Background:: Several studies have suggested potential aptitude of polylactic-co-glycolic acid (PLGA)-derived nanoparticles (NPs) to improve the antitumor efficacy of anticancer drugs against colon cancer. Further, conjugation of lectins over the surface of the NPs may ameliorate interaction and thus enhance attachment of NPs with receptors. Objective:: The main goal of the study was to prepare and evaluate targeting potential (in vivo) of the optimized NPs against colorectal cancer. Methods:: The 5-fluorouracil (5-FU) loaded and wheat germ agglutinin (WGA)-conjugated PLGA-NPs (WFUNPs) were prepared and then they were evaluated in vivo for targeting aptitude of formulation using gamma scintigraphy after oral delivery. The WGA-conjugated and non-conjugated optimized NPs were compared for any significant results. Further, optimized formulations were also assessed for different parameters such as radiolabeling efficiency, sodium pertechnetate uptake, stability of NPs, and organ distribution study. Results:: Findings suggested prolonged retention of 99mTc-tagged WFUNPs in the colonic region after 24 h study. Eventually, the outcome from conjugated formulation revealed enhanced bioavailability of the drug in blood plasma for up to 24 h. Conclusion:: In conclusion, WGA-conjugation to NPs could improve the performance of the PLGA-NPs in the treatment of colorectal cancer.


2021 ◽  
pp. 039139882110255
Author(s):  
Sara Anajafi ◽  
Azam Ranjbar ◽  
Monireh Torabi-Rahvar ◽  
Naser Ahmadbeigi

Background: Sufficient blood vessel formation in bioengineered tissues is essential in order to keep the viability of the organs. Impaired development of blood vasculatures results in failure of the implanted tissue. The cellular source which is seeded in the scaffold is one of the crucial factors involved in tissue engineering methods. Materials and methods: Considering the notable competence of Bone Marrow derived Mesenchymal Stem Cell aggregates for tissue engineering purposes, in this study BM-aggregates and expanded BM-MSCs were applied without any inductive agent or co-cultured cells, in order to investigate their own angiogenesis potency in vivo. BM-aggregates and BM-MSC were seeded in Poly-L Lactic acid (PLLA) scaffold and implanted in the peritoneal cavity of mice. Result: Immunohistochemistry results indicated that there was a significant difference ( p < 0.050) in CD31+ cells between PLLA scaffolds contained cultured BM-MSC; PLLA scaffolds contained BM-aggregates and empty PLLA. According to morphological evidence, obvious connections with recipient vasculature and acceptable integration with surroundings were established in MSC and aggregate-seeded scaffolds. Conclusion: Our findings revealed cultured BM-MSC and BM-aggregates, capacity in order to develop numerous connections between PLLA scaffold and recipient’s vasculature which is crucial to the survival of tissues, and considerable tendency to develop constructs containing CD31+ endothelial cells which can contribute in vessel’s tube formation.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii214-ii214
Author(s):  
Jenna Minami ◽  
Nicholas Bayley ◽  
Christopher Tse ◽  
Henan Zhu ◽  
Danielle Morrow ◽  
...  

Abstract Metabolic reprogramming is a hallmark of cancer, and malignant cells must acquire metabolic adaptations to fuel neoplastic progression. Mutations or changes in metabolic gene expression can impose nutrient dependencies in tumors, and even in the absence of metabolic defects, cancer cells can become auxotrophic for particular nutrients or metabolic byproducts generated by other cells in the tumor microenvironment (TME). Conventional cell lines do not recapitulate the metabolic heterogeneity of glioblastoma (GBM), while primary cultured cells do not account for the influences of the microenvironment and the blood brain barrier on tumor biology. Additionally, these systems are under strong selective pressure divergent from that in vivo, leading to reduced heterogeneity between cultured tumor cells. Here, we describe a biobank of direct-from-patient derived orthotopic xenografts (GliomaPDOX) and gliomaspheres that reveal a subset of gliomas that, while able to form in vivo, cannot survive in vitro. RNA sequencing of tumors that can form both in vivo and in vitro (termed “TME-Indifferent”) compared to that of tumors that can only form in vivo (termed “TME-Dependent”) revealed transcriptional changes associated with altered nutrient availability, emphasizing the unique metabolic programs impacted by the tumor microenvironment. Furthermore, TME-dependent tumors lack metabolic signatures associated with nutrient biosynthesis, thus indicating a potential dependency of these tumors on scavenging specific nutrients from the extracellular milieu. Collectively, these data emphasize the metabolic heterogeneity within GBM, and reveal a subset of gliomas that lack metabolic plasticity, indicating a potential brain-microenvironment specific metabolic dependency that can be targeted for therapy.


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