scholarly journals Trastuzumab Modified Barium Ferrite Magnetic Nanoparticles Labeled with Radium-223: A New Potential Radiobioconjugate for Alpha Radioimmunotherapy

Nanomaterials ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 2067
Author(s):  
Weronika Gawęda ◽  
Marek Pruszyński ◽  
Edyta Cędrowska ◽  
Magdalena Rodak ◽  
Agnieszka Majkowska-Pilip ◽  
...  
Keyword(s):  
Barium Ferrite ◽  
Magnetic Field Gradient ◽  
Hydrodynamic Diameter ◽  
Nuclear Space ◽  
Her2 Receptor ◽  
Ovarian Adenocarcinoma ◽  
Cell Monolayers ◽  
Cell Internalization ◽  
Radium 223 ◽  
High Cytotoxicity

Barium ferrite nanoparticles (BaFeNPs) were investigated as vehicles for 223Ra radionuclide in targeted α-therapy. BaFe nanoparticles were labeled using a hydrothermal Ba2+ cations replacement by 223Ra with yield reaching 61.3 ± 1.8%. Radiolabeled nanoparticles were functionalized with 3-phosphonopropionic acid (CEPA) linker followed by covalent conjugation to trastuzumab (Herceptin®). Thermogravimetric analysis and radiometric method with the use of [131I]-labeled trastuzumab revealed that on average 19–21 molecules of trastuzumab are attached to the surface of one BaFe–CEPA nanoparticle. The hydrodynamic diameter of BaFe–CEPA–trastuzumab conjugate is 99.9 ± 3.0 nm in water and increases to 218.3 ± 3.7 nm in PBS buffer, and the zeta potential varies from +27.2 ± 0.7 mV in water to −8.8 ± 0.7 in PBS buffer. The [223Ra]BaFe–CEPA–trastuzumab radiobioconjugate almost quantitatively retained 223Ra (>98%) and about 96% of 211Bi and 94% of 211Pb over 30 days. The obtained radiobioconjugate exhibited high affinity, cell internalization and cytotoxicity towards the human ovarian adenocarcinoma SKOV-3 cells overexpressing HER2 receptor. Confocal studies indicated that [223Ra]BaFe–CEPA–trastuzumab was located in peri-nuclear space. High cytotoxicity of the [223Ra]BaFe–CEPA–trastuzumab bioconjugate was confirmed by radiotoxicity studies on SKOV-3 cell monolayers and 3D-spheroids. In addition, the magnetic properties of the radiobioconjugate should allow for its use in guide drug delivery driven by magnetic field gradient.

scholarly journals Oral Pharmacokinetics of a Chitosan-Based Nano- Drug Delivery System of Interferon Alpha

Polymers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1862 ◽  
Author(s):  
Julieta C. Imperiale ◽  
Inbar Schlachet ◽  
Marianela Lewicki ◽  
Alejandro Sosnik ◽  
Mirna M. Biglione
Keyword(s):  
Interferon Alpha ◽  
Viral Infections ◽  
Chitosan Nanoparticles ◽  
Area Under The Curve ◽  
Hydrodynamic Diameter ◽  
Cell Compatibility ◽  
Cell Monolayers ◽  
Pegylated Nanoparticles ◽  
Oral Pharmacokinetics ◽  
Poly Ethylene

Interferon alpha (IFNα) is a protein drug used to treat viral infections and cancer diseases. Due to its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability, which is associated with severe side effects. We hypothesized that the nanoencapsulation of IFNα within nanoparticles of the mucoadhesive polysaccharide chitosan would improve the oral bioavailability of this drug. In this work, we produced IFNα-loaded chitosan nanoparticles by the ionotropic gelation method. Their hydrodynamic diameter, polydispersity index and concentration were characterized by dynamic light scattering and nanoparticle tracking analysis. After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability of unmodified and poly(ethylene glycol) (PEG)-modified (PEGylated) nanoparticles was measured in monoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated that the nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the study of the oral pharmacokinetics of nanoencapsulated IFNα in BalbC mice revealed two maxima and area-under-the-curve of 56.9 pg*h/mL.

scholarly journals Influence of the chirality of carbon nanodots on their interaction with proteins and cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huijie Yan ◽  
Michele Cacioppo ◽  
Saad Megahed ◽  
Francesca Arcudi ◽  
Luka Đorđević ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Colloidal Stability ◽  
Biological Effects ◽  
Biological Behavior ◽  
Carbon Nanodots ◽  
Hydrodynamic Diameter ◽  
Concentration Determination ◽  
Cell Internalization ◽  
Biological Phenomena ◽  
Opposite Chirality

AbstractCarbon nanodots with opposite chirality possess the same major physicochemical properties such as optical features, hydrodynamic diameter, and colloidal stability. Here, a detailed analysis about the comparison of the concentration of both carbon nanodots is carried out, putting a threshold to when differences in biological behavior may be related to chirality and may exclude effects based merely on differences in exposure concentrations due to uncertainties in concentration determination. The present study approaches this comparative analysis evaluating two basic biological phenomena, the protein adsorption and cell internalization. We find how a meticulous concentration error estimation enables the evaluation of the differences in biological effects related to chirality.

A pre-embedding, protein a-gold immunolabelling technique for cytocentrifuged cell monolayers for lm and tem

1986 ◽  
Vol 44 ◽  
pp. 220-221
Author(s):  
K. Chien ◽  
I.P. Shintaku ◽  
A.F. Sassoon ◽  
R.L. Van de Velde ◽  
R. Heusser
Keyword(s):  
Cell Surface ◽  
Staining Method ◽  
Protein A ◽  
Surface Antigens ◽  
Cell Suspensions ◽  
Cellular Morphology ◽  
Cellular Phenotype ◽  
Cell Surface Antigens ◽  
Cell Monolayers ◽  
Diagnostic Histopathology

Identification of cellular phenotype by cell surface antigens in conjunction with ultrastructural analysis of cellular morphology can be a useful tool in the study of biologic processes as well as in diagnostic histopathology. In this abstract, we describe a simple pre-embedding, protein A-gold staining method which is designed for cell suspensions combining the handling convenience of slide-mounted cell monolayers and the ability to evaluate specimen staining specificity prior to EM embedding.

Processing Immunoperoxidase Labeled Cell Monolayers and Cryostat Sesctions For Electron Microscopy

1985 ◽  
Vol 43 ◽  
pp. 714-715
Author(s):  
K. Chien ◽  
R. Van de Velde ◽  
I.P. Shintaku ◽  
A.F. Sassoon
Keyword(s):  
Cell Monolayer ◽  
Cell Types ◽  
Surface Antigens ◽  
Immunoperoxidase Method ◽  
Reaction Step ◽  
Hot Plate ◽  
Air Drying ◽  
New Approach ◽  
Cell Monolayers ◽  
Glass Slides

Immunoelectron microscopy of neoplastic lymphoma cells is valuable for precise localization of surface antigens and identification of cell types. We have developed a new approach in which the immunohistochemical staining can be evaluated prior to embedding for EM and desired area subsequently selected for ultrathin sectioning.A freshly prepared lymphoma cell suspension is spun onto polylysine hydrobromide- coated glass slides by cytocentrifugation and immediately fixed without air drying in polylysine paraformaldehyde (PLP) fixative. After rinsing in PBS, slides are stained by a 3-step immunoperoxidase method. Cell monolayer is then fixed in buffered 3% glutaraldehyde prior to DAB reaction. After the DAB reaction step, wet monolayers can be examined under LM for presence of brown reaction product and selected monolayers then processed by routine methods for EM and embedded with the Chien Re-embedding Mold. After the polymerization, the epoxy blocks are easily separated from the glass slides by heatingon a 100°C hot plate for 20 seconds.

Spectroscopic imaging of human disease

1996 ◽  
Vol 54 ◽  
pp. 884-885
Author(s):  
D.J. Meyerhoff
Keyword(s):  
Magnetic Field ◽  
Magnetic Resonance ◽  
Field Gradient ◽  
Human Disease ◽  
Morphological Changes ◽  
Magnetic Field Gradient ◽  
Spectroscopic Imaging ◽  
Resonance Spectroscopy ◽  
Tissue Water

Magnetic Resonance Imaging (MRI) observes tissue water in the presence of a magnetic field gradient to study morphological changes such as tissue volume loss and signal hyperintensities in human disease. These changes are mostly non-specific and do not appear to be correlated with the range of severity of a certain disease. In contrast, Magnetic Resonance Spectroscopy (MRS), which measures many different chemicals and tissue metabolites in the millimolar concentration range in the absence of a magnetic field gradient, has been shown to reveal characteristic metabolite patterns which are often correlated with the severity of a disease. In-vivo MRS studies are performed on widely available MRI scanners without any “sample preparation” or invasive procedures and are therefore widely used in clinical research. Hydrogen (H) MRS and MR Spectroscopic Imaging (MRSI, conceptionally a combination of MRI and MRS) measure N-acetylaspartate (a putative marker of neurons), creatine-containing metabolites (involved in energy processes in the cell), choline-containing metabolites (involved in membrane metabolism and, possibly, inflammatory processes),

Transport in Caco-2 cell monolayers of cucurbitane triterpenoids from Momordica charantia

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
SB Wu ◽  
GGL Yue ◽  
AC Keller ◽  
MH To ◽  
CBS Lau ◽  
...  
Keyword(s):  
Momordica Charantia ◽  
Cell Monolayers

Radionuklidtherapie im Behandlungskonzept von Knochenmetastasen

2014 ◽  
Vol 23 (04) ◽  
pp. 269-274
Author(s):  
M. Müller ◽  
T. Todenhöfer
Keyword(s):  
Radium 223

ZusammenfassungDie durch Knochenmetastasen hervorgerufenen Komplikationen und Schmerzen führen zu einer erheblichen Beeinträchtigung der Lebensqualität. Im Rahmen eines multimodalen Therapiekonzeptes für die Behandlung von Knochenmetastasen ist eine effektive Analgesie unverzichtbar. β-Strahler wie Strontium-89-Chlorid und Samarium- 153-EDTMP können vor allem bei Patienten mit osteoblastisch metastasierten Tumoren eine signifikante Schmerzreduktion erzielen. Die mit der Substanzgruppe verbundene Hämatotoxizität hat jedoch bisher zu einem zurückhaltenden Einsatz der Substanzen geführt. Des Weiteren ist diese Zurückhaltung auch auf die geringe Anzahl an prospektiv randomisierten Studien zurückzuführen. Für den β-Strahler Radium-223-Chlorid konnte in einer großen randomisierten Studie neben einer Schmerzreduktion eine Verlängerung des medianen Gesamtüberlebens von Patienten mit kastrationsrefraktärem Prostatakarzinom um 2,8 Monate (14 vs. 11,2 Monate im Placeboarm) beobachtet werden. Diese Effekte waren mit einer im Vergleich zu β-Strahlern deutlich niedrigeren Hämatotoxizität assoziiert. Die vielversprechenden Ergebnisse von Radium-223-Chlorid lassen einen vermehrten Einsatz von Radionukliden bei Patienten mit Prostatakarzinom erwarten.

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