scholarly journals Oxidation- and Temperature-Responsive Poly(hydroxyethyl acrylate-co-phenyl vinyl sulfide) Micelle as a Potential Anticancer Drug Carrier

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 462 ◽  
Author(s):  
Kim ◽  
Alle ◽  
Kim

Poly(hydroxyethyl acrylate-co-phenyl vinyl sulfide) (P(HEA-co-PVS)), as an oxidizable amphiphilic polymer, was prepared for the fabrication of an oxidation- and temperature-responsive micelle for the delivery of doxorubicin (DOX). The interfacial activity of H2O2-treated P(HEA-co-PVS) was significantly lower than that of the untreated variety, possibly because of the oxidization of PVS. P(HEA-co-PVS) exhibited a lower critical solution temperature (LCST) behavior and the LCST increased upon H2O2 treatment. The copolymer micelles, prepared by the dialysis method, were found to be round particles (less than 100 nm) on TEM micrograph. The release degree of Nile red loaded in the micelles was higher when the H2O2 concentration was higher, possibly because the micelles could be solubilized more readily at a higher H2O2 concentration. The release degree was more strongly dependent on the oxidizing agent concentration when the temperature was higher. DOX loaded in the micelles suppressed the in vitro growth of KB cells (a human cancer cell type originating from the cervix) much more effectively than DOX loaded in an unoxidizable control micelle and free DOX, possibly because the copolymer would undergo an increase in its LCST, lose its amphiphilic property, and the micelles would be disassembled. The DOX-loaded micelles were readily internalized into KB cells, as evidenced by flow cytometry (FACS) and confocal laser scanning microscopy (CLSM).

2008 ◽  
Vol 8 (6) ◽  
pp. 3085-3090 ◽  
Author(s):  
Akihiro Hayama ◽  
Tatsuhiro Yamamoto ◽  
Masayuki Yokoyama ◽  
Kumi Kawano ◽  
Yoshiyuki Hattori ◽  
...  

A novel technique was developed for the formation of ligand-targeted polymeric micelles that can be applicable to various ligands. For tumor-specific drug delivery, camptothecin (CPT)-loaded polymeric micelles were modified by folate to produce a folate-receptor-targeted drug carrier. Folate-linked PEG5000-distearoylphosphatidylethanolamine (folate-PEG5000-DSPE) was added when preparations of drug-loaded polymeric micelles, resulting in folate ligands exposed to the surface. Folate-modified CPT-loaded polymeric micelles (F-micelle) were evaluated by measuring cellular uptake using a flow cytometer, fluorescence microscopy, and confocal laser scanning microscopy, and by cytotoxicity measurement. The results revealed that F-micelle showed higher cellular uptake in KB cells over-expressing folate receptor (FR) and higher cytotoxicity compared with non-folate modified CPT-loaded polymeric micelles (plain micelles) in KB cells, but not in FR-negative HepG2 cells. This result indicated that polymeric micelles were successfully modified by the folate-linked lipid.


2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Zehua Liu ◽  
Shaoheng Tang ◽  
Zhiran Xu ◽  
Yingjun Wang ◽  
Xuan Zhu ◽  
...  

For preventing premature drug release in neutral environment and avoiding them being trapped into the endosomal/lysosomal system, we developed a novel iron silicate@liposome hybrid (ILH) formulation, which can be used as a carrier to transport doxorubicin (DOX) in a pH-sensitive manner and to escape from endosomal/lysosomal trapping through “proton-sponge” effect. The high intensity of photoacoustic signal fromin vitrophotoacoustic imaging (PAI) experiments suggests that it is a promising candidate for PAI agent, providing the potential for simultaneously bioimaging and cancer-targeting drug delivery. Cytotoxicity of our formulation toward tumor cells was remarkably higher than free DOX (48.4±7.7% and26.2±8.4%,P<0.001). Confocal laser scanning microscopy experiments showed the enhanced transportation and enrichment process of DOX in QSG-7703 cells. Taking together, we developed an easy approach to construct a multifunctional anticancer drug delivery/imaging system with a potency as a PAI agent. The strategy of combining drug carrier and imaging agent is an emerging platform for further construction of nanoparticle and may play a significant role in cancer therapy and diagnosis.


Materials ◽  
2020 ◽  
Vol 13 (14) ◽  
pp. 3235 ◽  
Author(s):  
Guoqiao Zhou ◽  
Bokai Zhang ◽  
Liyu Wei ◽  
Han Zhang ◽  
Massimiliano Galluzzi ◽  
...  

Plasticity and functional diversity of macrophages play an important role in resisting pathogens invasion, tumor progression and tissue repair. At present, nanodrug formulations are becoming increasingly important to induce and control the functional diversity of macrophages. In this framework, the internalization process of nanodrugs is co-regulated by a complex interplay of biochemistry, cell physiology and cell mechanics. From a biophysical perspective, little is known about cellular mechanics’ modulation induced by the nanodrug carrier’s internalization. In this study, we used the polylactic-co-glycolic acid (PLGA)–polyethylene glycol (PEG) nanofibers as a model drug carrier, and we investigated their influence on macrophage mechanics. Interestingly, the nanofibers internalized in macrophages induced a local increase of stiffness detected by atomic force microscopy (AFM) nanomechanical investigation. Confocal laser scanning microscopy revealed a thickening of actin filaments around nanofibers during the internalization process. Following geometry and mechanical properties by AFM, indentation experiments are virtualized in a finite element model simulation. It turned out that it is necessary to include an additional actin wrapping layer around nanofiber in order to achieve similar reaction force of AFM experiments, consistent with confocal observation. The quantitative investigation of actin reconfiguration around internalized nanofibers can be exploited to develop novel strategies for drug delivery.


Author(s):  
Trâm Trương Lê Bích

This article shows that the supramolecular micelle assemblies from PCL-b-P4VP block copolymers with α-CD via self-assembly of inclusion complexes in an aqueous solution. Dox encapsulation and the release at different pH of supramolecular micelle assemblies from poly (ε-caprolactone-block-4-vinylpyridine) (PCL-b-P4VP) block copolymers with α-CD showed excellent cytocompatibility. Dox was successfully loaded into the micelles with a loading content of 14.4% and loading efficiency of 28.9% by using UV-Vis spectroscopy (UV). The Dox loaded micelles showed lower cytotoxicity than free drugs, and could efficiently deliver and release the drug into human hepatocellular carcinoma (Hep-G2) cells as confirmed by confocal laser scanning microscopy (CLSM). These properties make the polymer micelles attractive as drug carriers for pharmaceutical applications.


Author(s):  
Thomas M. Jovin ◽  
Michel Robert-Nicoud ◽  
Donna J. Arndt-Jovin ◽  
Thorsten Schormann

Light microscopic techniques for visualizing biomolecules and biochemical processes in situ have become indispensable in studies concerning the structural organization of supramolecular assemblies in cells and of processes during the cell cycle, transformation, differentiation, and development. Confocal laser scanning microscopy offers a number of advantages for the in situ localization and quantitation of fluorescence labeled targets and probes: (i) rejection of interfering signals emanating from out-of-focus and adjacent structures, allowing the “optical sectioning” of the specimen and 3-D reconstruction without time consuming deconvolution; (ii) increased spatial resolution; (iii) electronic control of contrast and magnification; (iv) simultanous imaging of the specimen by optical phenomena based on incident, scattered, emitted, and transmitted light; and (v) simultanous use of different fluorescent probes and types of detectors.We currently use a confocal laser scanning microscope CLSM (Zeiss, Oberkochen) equipped with 3-laser excitation (u.v - visible) and confocal optics in the fluorescence mode, as well as a computer-controlled X-Y-Z scanning stage with 0.1 μ resolution.


Author(s):  
M. H. Chestnut ◽  
C. E. Catrenich

Helicobacter pylori is a non-invasive, Gram-negative spiral bacterium first identified in 1983, and subsequently implicated in the pathogenesis of gastroduodenal disease including gastritis and peptic ulcer disease. Cytotoxic activity, manifested by intracytoplasmic vacuolation of mammalian cells in vitro, was identified in 55% of H. pylori strains examined. The vacuoles increase in number and size during extended incubation, resulting in vacuolar and cellular degeneration after 24 h to 48 h. Vacuolation of gastric epithelial cells is also observed in vivo during infection by H. pylori. A high molecular weight, heat labile protein is believed to be responsible for vacuolation and to significantly contribute to the development of gastroduodenal disease in humans. The mechanism by which the cytotoxin exerts its effect is unknown, as is the intracellular origin of the vacuolar membrane and contents. Acridine orange is a membrane-permeant weak base that initially accumulates in low-pH compartments. We have used acridine orange accumulation in conjunction with confocal laser scanning microscopy of toxin-treated cells to begin probing the nature and origin of these vacuoles.


TAPPI Journal ◽  
2010 ◽  
Vol 9 (10) ◽  
pp. 7-15
Author(s):  
HANNA KOIVULA ◽  
DOUGLAS BOUSFIELD ◽  
MARTTI TOIVAKKA

In the offset printing process, ink film splitting has an important impact on formation of ink filaments. The filament size and its distribution influence the leveling of ink and hence affect ink setting and the print quality. However, ink filaments are difficult to image due to their short lifetime and fine length scale. Due to this difficulty, limited work has been reported on the parameters that influence filament size and methods to characterize it. We imaged ink filament remains and quantified some of their characteristics by changing printing speed, ink amount, and fountain solution type. Printed samples were prepared using a laboratory printability tester with varying ink levels and operating settings. Rhodamine B dye was incorporated into fountain solutions to aid in the detection of the filaments. The prints were then imaged with a confocal laser scanning microscope (CLSM) and images were further analyzed for their surface topography. Modeling of the pressure pulses in the printing nip was included to better understand the mechanism of filament formation and the origin of filament length scale. Printing speed and ink amount changed the size distribution of the observed filament remains. There was no significant difference between fountain solutions with or without isopropyl alcohol on the observed patterns of the filament remains.


2012 ◽  
Vol 11 (3) ◽  
pp. 669-674 ◽  
Author(s):  
Szabolcs Szilveszter ◽  
Botond Raduly ◽  
Szilard Bucs ◽  
Beata Abraham ◽  
Szabolcs Lanyi ◽  
...  

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