scholarly journals In vitro Cytotoxicity Studies of Industrially Used Common Nanomaterials on L929 and 3T3 Fibroblast Cells

2020 ◽  
Vol 1 (5) ◽  
pp. 192-200
Author(s):  
Madhulika Srikanth ◽  
Waseem S Khan ◽  
Ramazan Asmatulu ◽  
Heath E Misak ◽  
Shang-You Yang ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Cell Types ◽  
In Vitro Cytotoxicity ◽  
In Vitro Tests ◽  
Fibroblast Cells ◽  
In Vivo Experiments ◽  
Cytotoxicity Studies ◽  
Biomedical Electronics

The unique structures and properties of nanomaterials have attracted many engineers and scientists to these resources for different applications, including biomedical, electronics, manufacturing, transportation, energy, and defense. The increasing applications of nanomaterials have also caused some concern among the scientific community about their safety and cytotoxicity. To successfully use nanomaterials in different fields, their interaction with mammalian cells in vitro must be addressed before in vivo experiments can be carried out successfully. In this study, the cytotoxicity values of commonly known nanomaterials, such as 100-ply Carbon Nanotube (CNT) wires, graphene, CNTs, nanoclay, and fullerene, were investigated through in vitro tests on human L929 and mice 3T3 fibroblast cells and compared with each other. The effects of cytotoxicity on both cell types were similar in many ways, but not closely identical due to structural and morphological differences. Compared to mice fibroblast cells, human fibroblast cells have a larger surface area; therefore, the viability values of L929 cells at different dilutions and time durations vary over a larger range. Pristine 100-ply CNT wires were found to be the least cytotoxic, with an average viability of 86.9%, whereas materials with high aspect ratio (e.g., CNTs and graphene) had higher cytotoxicity values due to their potential to pierce through cell membranes.

scholarly journals Activity of Indenoisoquinolines against African Trypanosomes

2008 ◽  
Vol 53 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Rahul P. Bakshi ◽  
Dongpei Sang ◽  
Andrew Morrell ◽  
Mark Cushman ◽  
Theresa A. Shapiro
Keyword(s):  
Anticancer Agents ◽  
Mammalian Cells ◽  
Sleeping Sickness ◽  
Water Soluble ◽  
African Trypanosomes ◽  
In Vivo Experiments ◽  
Topoisomerase Ib ◽  
Topoisomerase Poisons

ABSTRACT African trypanosomiasis (sleeping sickness), caused by protozoan Trypanosoma brucei species, is a debilitating disease that is lethal if untreated. Available drugs are antiquated, toxic, and compromised by emerging resistance. The indenoisoquinolines are a class of noncamptothecin topoisomerase IB poisons that are under development as anticancer agents. We tested a variety of indenoisoquinolines for their ability to kill T. brucei. Indenoisoquinolines proved trypanocidal at submicromolar concentrations in vitro. Structure-activity analysis yielded motifs that enhanced potency, including alkylamino substitutions on N-6, methoxy groups on C-2 and C-3, and a methylenedioxy bridge between C-8 and C-9. Detailed analysis of eight water-soluble indenoisoquinolines demonstrated that in trypanosomes the compounds inhibited DNA synthesis and acted as topoisomerase poisons. Testing these compounds on L1210 mouse leukemia cells revealed that all eight were more effective against trypanosomes than against mammalian cells. In preliminary in vivo experiments one compound delayed parasitemia and extended survival in mice subjected to a lethal trypanosome challenge. The indenoisoquinolines provide a promising lead for the development of drugs against sleeping sickness.

Polymeric/Inorganic Multifunctional Nanoparticles for Simultaneous Drug Delivery and Visualization

2010 ◽  
Vol 1257 ◽  
Author(s):  
Andrea Fornara ◽  
Alberto Recalenda ◽  
Jian Qin ◽  
Abhilash Sugunan ◽  
Fei Ye ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluorescence Microscopy ◽  
Contrast Agents ◽  
Gold Nanorods ◽  
In Vitro Cytotoxicity ◽  
In Vivo Studies ◽  
Multifunctional Nanoparticles ◽  
Cytotoxicity Studies

AbstractNanoparticles consisting of different biocompatible materials are attracting a lot of interest in the biomedical area as useful tools for drug delivery, photo-therapy and contrast enhancement agents in MRI, fluorescence and confocal microscopy. This work mainly focuses on the synthesis of polymeric/inorganic multifunctional nanoparticles (PIMN) based on biocompatible di-block copolymer poly(L,L-lactide-co-ethylene glycol) (PLLA-PEG) via an emulsion-evaporation method. Besides containing a hydrophobic drug (Indomethacin), these polymeric nanoparticles incorporate different visualization agents such as superparamagnetic iron oxide nanoparticles (SPION) and fluorescent Quantum Dots (QDs) that are used as contrast agents for Magnetic Resonance Imaging (MRI) and fluorescence microscopy together. Gold Nanorods are also incorporated in such nanostructures to allow simultaneous visualization and photodynamic therapy. MRI studies are performed with different loading of SPION into PIMN, showing an enhancement in T2 contrast superior to commercial contrast agents. Core-shell QDs absorption and emission spectra are recorded before and after their loading into PIMN. With these polymeric/inorganic multifunctional nanoparticles, both MRI visualization and confocal fluorescence microscopy studies can be performed. Gold nanorods are also synthesized and incorporated into PIMN without changing their longitudinal absorption peak usable for lased excitation and phototherapy. In-vitro cytotoxicity studies have also been performed to confirm the low cytotoxicity of PIMN for further in-vivo studies.

scholarly journals Postprandial transfer of colostral extracellular vesicles and their protein and miRNA cargo in neonatal calves

2019 ◽  
Author(s):  
Benedikt Kirchner ◽  
Dominik Buschmann ◽  
Vijay Paul ◽  
Michael W. Pfaffl
Keyword(s):  
Extracellular Vesicles ◽  
Expression Profiles ◽  
Bovine Milk ◽  
Cell Types ◽  
Specific Protein ◽  
In Vivo Experiments ◽  
Neonatal Calves ◽  
Almost All

Abstract Background Extracellular vesicles (EVs) such as exosomes are key regulators of intercellular communication that can be found in almost all bio fluids. Although studies in the last decade have made great headway in discerning the role of EVs in many physiological and pathophysiological processes, the bioavailability and impact of dietary EVs and their cargo still remain to be elucidated. Due to its widespread consumption and high content of EV-associated microRNAs and proteins, a major focus in this field has been set on EVs in bovine milk and colostrum. Despite promising in vitro studies in recent years that show high resiliency of milk EVs to degradation and uptake of milk EV cargo in a variety of intestinal and blood cell types, in vivo experiments continue to be inconclusive and sometimes outright contradictive. Results To resolve this discrepancy, we assessed the potential postprandial transfer of colostral EVs to the circulation of newborn calves by analysing colostrum-specific protein and miRNAs, including specific isoforms (isomiRs) in cells, EV isolations and unfractionated samples from blood and colostrum. Our findings reveal distinct populations of EVs in colostrum and blood from cows that can be clearly separated by density, particle concentration and protein content (BTN1A1, MFGE8). Postprandial blood samples of calves show a time-dependent increase in EVs that share morphological and protein characteristics of colostral EVs. Analysis of miRNA expression profiles by Next-Generation Sequencing gave a different picture however. Although significant postprandial expression changes could only be detected for calf EV samples, expression profiles show very limited overlap with highly expressed miRNAs in colostral EVs or colostrum in general. Conclusions Taken together our results indicate a selective uptake of membrane-associated protein cargo but not luminal miRNAs from colostral EVs into the circulation of neonatal calves.

scholarly journals Serotherapy of B-cell neoplasms with anti-B4-blocked ricin: a phase I trial of daily bolus infusion

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 576-585 ◽  
Author(s):  
ML Grossbard ◽  
AS Freedman ◽  
J Ritz ◽  
F Coral ◽  
VS Goldmacher ◽  
...  
Keyword(s):  
Phase I ◽  
B Cell ◽  
Maximum Tolerated Dose ◽  
In Vitro Cytotoxicity ◽  
Bolus Infusion ◽  
Protein Toxin ◽  
Cytotoxicity Studies ◽  
Ricin A

Anti-B4-blocked Ricin (Anti-B4-bR) is an immunotoxin comprised of the anti-B4 monoclonal antibody (MoAb) and the protein toxin “blocked ricin.” The anti-B4 MoAb is directed against the B-lineage-restricted CD19 antigen expressed on more than 95% of normal and neoplastic B cells. Blocked ricin is an altered ricin derivative that has its nonspecific binding eliminated by chemically blocking the galactose binding domains of the B chain. In vitro cytotoxicity studies demonstrate that the IC37 of Anti-B4-bR is 2 x 10(-11) mol/L compared with 4 x 10(-12) mol/L for native ricin. A phase I dose escalation clinical trial was conducted in 25 patients with refractory B-cell malignancies. Anti-B4-bR was administered by daily 1-hour bolus infusion for 5 consecutive days at doses ranging from 1 microgram/kg/d to 60 micrograms/kg/d. Serum levels above 1 nmol/L were achieved transiently in the majority of patients treated at the maximum tolerated dose of 50 micrograms/kg/d for 5 days for a total dose of 250 micrograms/kg. The dose-limiting toxicity was defined by transient, reversible grade 3 elevations in hepatic transaminases, without impaired hepatic synthetic function. Minor toxicities included transient hypoalbuminemia, thrombocytopenia, and fevers. Human antimouse antibody and human anti-ricin antibody were detected in nine patients. One complete response, two partial responses, and eight mixed or transient responses were observed. These results show the in vitro and in vivo cytotoxicity of Anti-B4-bR and indicate that this immunotoxin can be administered as a daily bolus infusion for 5 days with tolerable, reversible toxicity.

scholarly journals Baculoviruses as Vectors for Gene Therapy against Human Prostate Cancer

2003 ◽  
Vol 2003 (2) ◽  
pp. 79-91 ◽  
Author(s):  
Lindsay J. Stanbridge ◽  
Vincent Dussupt ◽  
Norman J. Maitland
Keyword(s):  
Prostate Cancer ◽  
Gene Therapy ◽  
Viral Entry ◽  
Mammalian Cells ◽  
Primary Tumour ◽  
Genetic Material ◽  
Cell Types ◽  
Attractive Alternative

Current curative strategies for prostate cancer are restricted to the primary tumour, and the effect of treatments to control metastatic disease is not sustained. Therefore, the application of gene therapy to prostate cancer is an attractive alternative. Baculoviruses are highly restricted insect viruses, which can enter, but not replicate in mammalian cells. Baculoviruses can incorporate large amounts of extra genetic material, and will express transgenes in mammalian cells when under the control of a mammalian or strong viral promoter. Successful gene delivery has been achieved both in vitro and in vivo and into both dividing and nondividing cells, which is important since prostate cancers divide relatively slowly. In addition, the envelope protein gp64 is sufficiently mutable to allow targeted transduction of particular cell types. In this review, the advantages of using baculoviruses for prostate cancer gene therapy are explored, and the mechanisms of viral entry and transgene expression are described.

scholarly journals Preparation, Cytotoxicity, and In Vitro Bioimaging of Water Soluble and Highly Fluorescent Palladium Nanoclusters

2020 ◽  
Vol 7 (1) ◽  
pp. 20 ◽  
Author(s):  
Suresh Thangudu ◽  
Poliraju Kalluru ◽  
Raviraj Vankayala
Keyword(s):  
In Vitro Cytotoxicity ◽  
Molecular Probes ◽  
Water Soluble ◽  
Quantum Yields ◽  
Cell Labelling ◽  
Metal Nanoclusters ◽  
Extinction Coefficients ◽  
Cytotoxicity Studies

Fluorescent probes offer great potential to identify and treat surgical tumors by clinicians. To this end, several molecular probes were examined as in vitro and in vivo bioimaging probes. However, due to their ultra-low extinction coefficients as well as photobleaching problems, conventional molecular probes limit its practical utility. To address the above mentioned challenges, metal nanoclusters (MNCs) can serve as an excellent alternative with many unique features such as higher molar extinction coefficients/light absorbing capabilities, good photostability and appreciable fluorescence quantum yields. Herein, we reported a green synthesis of water soluble palladium nanoclusters (Pd NCs) and characterized them by using various spectroscopic and microscopic characterization techniques. These nanoclusters showed excellent photophysical properties with the characteristic emission peak centered at 500 nm under 420 nm photoexcitation wavelength. In vitro cytotoxicity studies in human cervical cancer cells (HeLa) cells reveal that Pd NCs exhibited good biocompatibility with an IC50 value of >100 µg/mL and also showed excellent co-localization and distribution throughout the cytoplasm region with a significant fraction translocating into cell nucleus. We foresee that Pd NCs will carry huge potential to serve as a new generation bioimaging nanoprobe owing to its smaller size, minimal cytotoxicity, nucleus translocation capability and good cell labelling properties.

scholarly journals Preparation and evaluation of chitosan based thermoreversible gels for intraperitoneal delivery of 5-fluorouracil (5-FU)

2013 ◽  
Vol 63 (4) ◽  
pp. 479-491 ◽  
Author(s):  
Bhavesh P. Depani ◽  
Anuja A. Naik ◽  
Hema A. Nair
Keyword(s):  
Antineoplastic Agent ◽  
In Vitro Cytotoxicity ◽  
In Vivo Studies ◽  
Comparable Efficacy ◽  
Prolonged Release ◽  
Fibroblast Cells ◽  
Glycerol Phosphate ◽  
Drug Free

Abstract Sterile thermoreversibly gelling systems based on chitosan- glycerol phosphate were developed for intraperitoneal delivery of the antineoplastic agent 5-FU. The formulation was evaluated for gelling characteristics and in vitro drug release. Drug free gels were evaluated for in vitro cytotoxicity in L-929 mouse fibroblast cells. Drug loaded gels were subjected to acute toxicity studies in Swiss albino mice via intraperitoneal route and efficacy studies via intratumoral injections in subcutaneous colon carcinoma bearing BALB/c mice. The formulations gelled reversibly in 8 min at 37 °C and provided prolonged release of the drug. Drug free systems showed dose dependent cytotoxicity in fibroblast cells, while in vivo studies revealed a 2.8-fold increase in LD50 of 5-FU administered intraperitoneally as the developed system. Tumor volume measurements showed comparable efficacy of 5-FU administered as gel and commercial injection with a greatly improved safety profile of the former as adjudged from mortality and body weight measurements.

scholarly journals In vivo animal models in periodontal research - focus on rodents

2021 ◽  
Vol 24 (2) ◽  
pp. 167-175
Author(s):  
E. I. Firkova
Keyword(s):  
Animal Models ◽  
Cellular Level ◽  
In Vitro Tests ◽  
Large Species ◽  
In Vivo Experiments ◽  
Data Translation ◽  
In Vivo Animal Models ◽  
Periodontal Research

Periodontal research has developed very fast in the last two decades. Although at this stage of science a lot of genetic and molecular-based trials are performed in order to elucidate the complex etiology, pathophysiology, biofilm-host interactions and responses on genetic and cellular level, in vivo animal models are still used. In many ways, in vivo experiments are superior to in vitro tests when the dynamics of the immune-inflammatory nature of the periodontal disease and peri-implantitis and the specific healing of soft and hard tissues is concerned. Screening the efficacy, mechanisms of action and application of different biomaterials requires in vivo experiments, be-fore the data translation to clinical settings. A number of small animals like rodents and large species like dogs and nonhuman primates are involved in periodontal research. As live creatures are used, the design of the studies must be well defined, with regard to the type of the animals, most suitable for the tested hypothesis, observation period, sample size, study power, critical size defects, and specific testing sites.

scholarly journals Infectious clone construction of dengue virus type 2, strain Jamaican 1409, and characterization of a conditional E6 mutation

2006 ◽  
Vol 87 (8) ◽  
pp. 2263-2268 ◽  
Author(s):  
Dennis J. Pierro ◽  
Ma Isabel Salazar ◽  
Barry J. Beaty ◽  
Ken E. Olson
Keyword(s):  
Cell Culture ◽  
Dengue Virus ◽  
Virus Type ◽  
Mammalian Cells ◽  
Infectious Clone ◽  
Cell Types ◽  
Dengue Virus Type 2

A full-length infectious cDNA clone (ic) was constructed from the genome of the dengue virus type 2 (DENV-2) Jamaica83 1409 strain, pBAC1409ic, by using a bacterial artifical chromosome plasmid system. Infectious virus was generated and characterized for growth in cell culture and for infection in Aedes aegypti mosquitoes. During construction, an isoleucine to methionine (Ile→Met) change was found at position 6 in the envelope glycoprotein sequence between low- and high-passage DENV-2 1409 strains. In vitro-transcribed genomic RNA of 1409ic with E6-Ile produced infectious virions following electroporation in mosquito cells, but not mammalian cells, while 1409ic RNA with an E6-Met mutation produced virus in both cell types. Moreover, DENV-2 1409 with the E6-Ile residue produced syncytia in C6/36 cell culture, whereas viruses with E6-Met did not. However, in vitro cell culture-derived growth-curve data and in vivo mosquito-infection rates revealed that none of the analysed DENV-2 strains differed from each other.

scholarly journals Serotherapy of B-cell neoplasms with anti-B4-blocked ricin: a phase I trial of daily bolus infusion

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 576-585 ◽  
Author(s):  
ML Grossbard ◽  
AS Freedman ◽  
J Ritz ◽  
F Coral ◽  
VS Goldmacher ◽  
...  
Keyword(s):  
Phase I ◽  
B Cell ◽  
Maximum Tolerated Dose ◽  
In Vitro Cytotoxicity ◽  
Bolus Infusion ◽  
Protein Toxin ◽  
Cytotoxicity Studies ◽  
Ricin A

Abstract Anti-B4-blocked Ricin (Anti-B4-bR) is an immunotoxin comprised of the anti-B4 monoclonal antibody (MoAb) and the protein toxin “blocked ricin.” The anti-B4 MoAb is directed against the B-lineage-restricted CD19 antigen expressed on more than 95% of normal and neoplastic B cells. Blocked ricin is an altered ricin derivative that has its nonspecific binding eliminated by chemically blocking the galactose binding domains of the B chain. In vitro cytotoxicity studies demonstrate that the IC37 of Anti-B4-bR is 2 x 10(-11) mol/L compared with 4 x 10(-12) mol/L for native ricin. A phase I dose escalation clinical trial was conducted in 25 patients with refractory B-cell malignancies. Anti-B4-bR was administered by daily 1-hour bolus infusion for 5 consecutive days at doses ranging from 1 microgram/kg/d to 60 micrograms/kg/d. Serum levels above 1 nmol/L were achieved transiently in the majority of patients treated at the maximum tolerated dose of 50 micrograms/kg/d for 5 days for a total dose of 250 micrograms/kg. The dose-limiting toxicity was defined by transient, reversible grade 3 elevations in hepatic transaminases, without impaired hepatic synthetic function. Minor toxicities included transient hypoalbuminemia, thrombocytopenia, and fevers. Human antimouse antibody and human anti-ricin antibody were detected in nine patients. One complete response, two partial responses, and eight mixed or transient responses were observed. These results show the in vitro and in vivo cytotoxicity of Anti-B4-bR and indicate that this immunotoxin can be administered as a daily bolus infusion for 5 days with tolerable, reversible toxicity.

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