The effect of ALA-PDT under normoxia and cobalt chloride (CoCl2)-induced hypoxia on adhesion molecules (ICAM-1, VCAM-1) secretion by colorectal cancer cells

Publication date: Available online 8 May 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Aleksandra Kawczyk-Krupka, Zenon Czuba, Beata Kwiatek, Sebastian Kwiatek, Magdalena Krupka, Karolina Sieroń
BACKGROUNDThe most fundamental problem in cancer biology research is to understand the mechanisms of cancer cell resistance to oncological therapies. Literature reports emphasize the important role of adhesion molecules: intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 (ICAM-1 and VCAM-1) in cancer progression and resistance to treatment. Photodynamic therapy (PDT) could become the component of a personalized approach to colorectal cancer, therefore we examined the effects of ALA (δ-aminolevulinic) acid PDT in normoxia and under cobalt chloride (CoCl2)-induced hypoxia on ICAM-1 and VCAM-1 secretion by colorectal cancer cells.METHODSHuman colorectal cancer cells of different malignant potential SW480 and SW620 were used in the experiment. Cell lines were treated ALA, in order to achieve conditions comparable to in vivo hypoxia, CoCl2 was added, then cells were irradiated both in normoxia and in hypoxia-like conditions. Cell viability was assessed using the LDH and MTT assays and apoptosis. ICAM-1 and VCAM-1 concentrations were determined with the Bio − Plex ProTM Assay and System.RESULTSThe experiment revealed that ALA PDT under normoxia and CoCl2-induced hypoxia had no significant effect on ICAM-1 and VCAM-1-dependent adhesion of colorectal cancer cells. The secretion of ICAM-1 by SW480 ell line was more pronounced compared to ICAM-1 secretion by SW620 cells.CONCLUSIONDetermination of tumor marker levels and especially adhesion molecules involved in metastatic spread is necessary. Our experiment reveals, that ALA PDT in normoxia and CoCl2-induced hypoxia has no effect on adhesion molecules secretion by colon cancer cells in vitro.



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An Update on Memory Reconsolidation Updating

Publication date: Available online 8 May 2017
Source:Trends in Cognitive Sciences
Author(s): Jonathan L.C. Lee, Karim Nader, Daniela Schiller
The reactivation of a stored memory in the brain can make the memory transiently labile. During the time it takes for the memory to restabilize (reconsolidate) the memory can either be reduced by an amnesic agent or enhanced by memory enhancers. The change in memory expression is related to changes in the brain correlates of long-term memory. Many have suggested that such retrieval-induced plasticity is ideally placed to enable memories to be updated with new information. This hypothesis has been tested experimentally, with a translational perspective, by attempts to update maladaptive memories to reduce their problematic impact. We review here progress on reconsolidation updating studies, highlighting their translational exploitation and addressing recent challenges to the reconsolidation field.



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Intramyocardial fate and effect of iron nanoparticles co-injected with MACS® purified stem cell products

Publication date: August 2017
Source:Biomaterials, Volume 135
Author(s): Paula Müller, Ralf Gaebel, Heiko Lemcke, Frank Wiekhorst, Frauke Hausburg, Cajetan Lang, Nicole Zarniko, Bernd Westphal, Gustav Steinhoff, Robert David
BackgroundMagnetic activated cell sorting (MACS^®) is routinely used to isolate stem cell subpopulations intended for the treatment of cardiovascular diseases. In strong contrast, studies examining the amount, effect and intramyocardial distribution of iron nanoparticles used for magnetic cell labelling are missing, although iron excess can cause functional disorders in the heart.Methods and resultsCD133⁺ haematopoietic and CD271⁺ mesenchymal stem cells were purified from bone marrow using automatically and manually MACS^® based systems. Flow cytometric measurements demonstrated a rapid loss of MACS^® MicroBeads from cells under culture conditions, while storage under hypothermic conditions decelerated their detachment. Moreover, an average loading of ∼11 fg iron/cell caused by magnetic labelling was determined in magnetic particle spectroscopy. Importantly, hemodynamic measurements as well as histological examinations using a myocardial ischemia/reperfusion mouse model showed no influence of MACS^® MicroBeads on cardiac regeneration, while the transplantation of stem cells caused a significant improvement. Furthermore, immunostainings demonstrated the clearance of co-injected iron nanoparticles from stem cells and the surrounding heart tissue within 48 h post transplantation.ConclusionsOur results indicate that iron amounts typically co-injected with MACS^® purified stem cells do not harm cardiac functions and are cleared from heart tissue within a few hours. Therefore, we conclude that MACS^® MicroBeads exhibit a good compatibility in the cardiac environment.



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High yield, scalable and remotely drug-loaded neutrophil-derived extracellular vesicles (EVs) for anti-inflammation therapy

Publication date: August 2017
Source:Biomaterials, Volume 135
Author(s): Jin Gao, Sihan Wang, Zhenjia Wang
Extracellular vesicles (EVs) are nanoscale membrane-formed compartments naturally secreted from cells, which are intercellular mediators regulating physiology and pathogenesis, therefore they could be a novel therapeutic carrier for targeted delivery. However, the translation of EVs is hindered by the heterogeneous composition, low yield, inefficient drug loading and unlikely scalability. Here we report a strategy to generate EVs using nitrogen cavitation (NC-EVs) that instantly disrupts neutrophils to form nanosized membrane vesicles. NC-EVs are similar to naturally secreted EVs (NS-EVs), but contain less subcellular organelles and nuclear acids. The production of NC-EVs was increased by 16 folds and is easy to scale up for clinical use compared to NS-EVs. To examine the usefulness of NC-EVs as a drug delivery platform, piceatannol (an anti-inflammation drug) was remotely loaded in NC-EVs via the pH gradient. We found that piceatannol-loaded NC-EVs dramatically alleviated acute lung inflammation/injury and sepsis induced by lipopolysaccharide (LPS). Our studies reveal that nitrogen cavitation is a novel approach to efficiently generate EVs from any cell type and could be exploited for personalized nanomedicine.



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Editorial board

Publication date: July 2017
Source:Biomaterials, Volume 134





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Natural healing-inspired collagen-targeting surgical protein glue for accelerated scarless skin regeneration

Publication date: July 2017
Source:Biomaterials, Volume 134
Author(s): Eun Young Jeon, Bong-Hyuk Choi, Dooyup Jung, Byeong Hee Hwang, Hyung Joon Cha
Skin scarring after deep dermal injuries is a major clinical problem due to the current therapies limited to established scars with poor understanding of healing mechanisms. From investigation of aberrations within the extracellular matrix involved in pathophysiologic scarring, it was revealed that one of the main factors responsible for impaired healing is abnormal collagen reorganization. Here, inspired by the fundamental roles of decorin, a collagen-targeting proteoglycan, in collagen remodeling, we created a scar-preventive collagen-targeting glue consisting of a newly designed collagen-binding mussel adhesive protein and a specific glycosaminoglycan. The collagen-targeting glue specifically bound to type I collagen in a dose-dependent manner and regulated the rate and the degree of fibrillogenesis. In a rat skin excisional model, the collagen-targeting glue successfully accelerated initial wound regeneration as defined by effective reepithelialization, neovascularization, and rapid collagen synthesis. Moreover, the improved dermal collagen architecture was demonstrated by uniform size of collagen fibrils, their regular packing, and a restoration of healthy tissue component. Collectively, our natural healing-inspired collagen-targeting glue may be a promising therapeutic option for improving the healing rate with high-quality and effective scar inhibition.



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Co and terpolymer reactivity ratios of chemically amplified resists

Publication date: 2 June 2017
Source:Polymer, Volume 118
Author(s): Narahari S. Pujari, Mingxing Wang, Kenneth E. Gonsalves
Resists are important multicomponent system require in microelectronic industry for fabrication of integrated circuit (IC) devices. The current high end IC (integrated circuit) technology node in manufacturing is 20 nm and looking toward 16 and 10 nm nodes to fulfil market demand. A series of chemically amplified resists (CARs) based on co and terpolymers of 4-hydroxystyrene (HOST), 2-ethyl-2-adamantyl methacrylate (EAMA) and/or a monomer-bound anionic photoacid generator (PAG) were prepared and characterized. Specifically, Triphenylsulfonium salt 4-(methacryloxy)-2,3,5,6-tetrafluorobenzenesulfonate (F4 PAG) was incorporated into the main chain to get PAG bound polymer microstructure.The aim of the study was to investigate interplay of individual monomers in co and terpolymer systems. This was achieved by understanding the reactivity ratios and monomer sequence distribution in the polymer. Analysis was conducted by using a software PROCOP version2.3. The co/terpolymer compositions were determined by quantitative ¹H NMR spectra. The copolymer reactivity ratio of each monomer was determined with Fineman–Ross, Kelen–Tüdös, and nonlinear least-squares curve- fitting methods. It was observed that EAMA is not polymerizable under given reaction conditions and copolymerization of EAMA-PAG was also not possible. HOST-EAMA system yielded reactivity ratios near zero indicating that they form quasi alternating structures. HOST-PAG system yielded copolymers rich in PAG. On the basis of the reactivity ratios determined from the binary copolymers, Alfrey–Goldfinger equations were used to estimate the compositions of the terpolymers. In terpolymer system, where two monomers were non homopolymerizable, both PAG and EAMA competed to add up to the HOST radical. All six reactivity values were less then unity indicating preferred cross propagation of radicals. PAG was the most reactive monomer. Monomer sequence distribution of copolymer and terpolymer was established to get an idea of detailed microstructure of the chain. Copolymers confirmed 84% of dyads formation of each monomer while terpolymer analysis revealed dominance of HOST centered triads. In addition to this, kinetics of terpolymerization reaction was performed to validate the theory. Findings from the study can be used to tailor make CAR synthesis for optimum EUV (extreme ultraviolet) lithography performance.

Graphical abstract

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