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Zilony N.,Bar - Ilan University | Zilony N.,Bar Ilan Institute of Nanotechnologies and Advanced Materials | Tzur-Balter A.,Technion - Israel Institute of Technology | Segal E.,Technion - Israel Institute of Technology | And 3 more authors.
Scientific Reports | Year: 2013

A new paradigm for an effective delivery of therapeutics into cancer cells is presented. Degradable porous silicon carriers, which are tailored to carry and release a model anti-cancer drug, are biolistically bombarded into in-vitro cancerous targets. We demonstrate the ability to launch these highly porous microparticles by a pneumatic capillary gene gun, which is conventionally used to deliver cargos by heavy metal carriers. By optimizing the gun parameters e.g., the accelerating gas pressure, we have successfully delivered the porous carriers, to reach deep targets and to cross a skin barrier in a highly spatial resolution. Our study reveals significant cytotoxicity towards the target human breast carcinoma cells following the delivery of drug-loaded carriers, while administrating empty particles results in no effect on cell viability. The unique combination of biolistics with the temporal control of payload release from porous carriers presents a powerful and non-conventional platform for designing new therapeutic strategies. Source


Baranes K.,Bar - Ilan University | Baranes K.,Bar Ilan Institute of Nanotechnologies and Advanced Materials | Kollmar D.,Bar - Ilan University | Kollmar D.,Yeshiva University | And 6 more authors.
Journal of Molecular Histology | Year: 2012

We study the effect of topographic nano-cues on neuronal growth-morphology using invertebrate neurons in culture. We use photolithography to fabricate substrates with repeatable line-pattern ridges of nano-scale heights of 10-150 nm. We plate leech neurons atop the patterned-substrates and compare their growth pattern to neurons plated atop non-patterned substrates. The model system allows us the analysis of single neurite-single ridge interactions. The use of high resolution electron microscopy reveals small filopodia processes that attach to the line-pattern ridges. These fine processes, that cannot be detected in light microscopy, add anchoring sites onto the side of the ridges, thus additional physical support. These interactions of the neuronal process dominantly affect the neuronal growth direction. We analyze the response of the entire neuronal branching tree to the patterned substrates and find significant effect on the growth patterns compared to non-patterned substrates. Moreover, interactions with the nano-cues trigger a growth strategy similarly to interactions with other neuronal cells, as reflected in their morphometric parameters. The number of branches and the number of neurites originating from the soma decrease following the interaction demonstrating a tendency to a more simplified neuronal branching tree. The effect of the nano-cues on the neuronal function deserves further investigation and will strengthen our understanding of the interplay between function and form. © Springer Science+Business Media B.V. 2012. Source


Baranes K.,Bar - Ilan University | Baranes K.,Bar Ilan Institute of Nanotechnologies and Advanced Materials | Chejanovsky N.,Bar Ilan Institute of Nanotechnologies and Advanced Materials | Chejanovsky N.,Bar - Ilan University | And 6 more authors.
Biotechnology and Bioengineering | Year: 2012

We study the role of nano-scale cues in controlling neuronal growth. We use photolithography to fabricate substrates with repeatable line-pattern ridges of nano-scale heights. We find that neuronal processes, which are of micron size, have strong interactions with ridges even as low as 10nm. The interaction between the neuronal process and the ridge leads to a deflection of growth direction and a preferred alignment with the ridges. The interaction strength clearly depends on the ridges' height. For 25nm ridges approximately half of the neuronal processes are modified, while at 100nm the majority of neurites change their original growth direction post interaction. In addition, the effect on growth correlates with the incoming angle between the neuronal process and the ridge. We underline the adhesion as a key mechanism in directing neuronal growth. Our study highlights the sensitivity of growing neurites to nano-scale cues thus opens a new avenue of research for pre-designed neuronal growth and circuitry. © 2012 Wiley Periodicals, Inc. Source


Marcus M.,Bar - Ilan University | Marcus M.,Bar Ilan Institute of Nanotechnologies and Advanced Materials | Skaat H.,Bar - Ilan University | Skaat H.,Bar Ilan Institute of Nanotechnologies and Advanced Materials | And 6 more authors.
Nanoscale | Year: 2015

The search for regenerative agents that promote neuronal differentiation and repair is of great importance. Nerve growth factor (NGF) which is an essential contributor to neuronal differentiation has shown high pharmacological potential for the treatment of central neurodegenerative diseases such as Alzheimer's and Parkinson's. However, growth factors undergo rapid degradation, leading to a short biological half-life. In our study, we describe a new nano-based approach to enhance the NGF activity resulting in promoted neuronal differentiation. We covalently conjugated NGF to iron oxide nanoparticles (NGF-NPs) and studied the effect of the novel complex on the differentiation of PC12 cells. We found that the NGF-NP treatment, at the same concentration as free NGF, significantly promoted neurite outgrowth and increased the complexity of the neuronal branching trees. Examination of neuronal differentiation gene markers demonstrated higher levels of expression in PC12 cells treated with the conjugated factor. By manipulating the NGF specific receptor, TrkA, we have demonstrated that NGF-NPs induce cell differentiation via the regular pathway. Importantly, we have shown that NGF-NPs undergo slower degradation than free NGF, extending their half-life and increasing NGF availability. Even a low concentration of conjugated NGF treatment has led to an effective response. We propose the use of the NGF-NP complex which has magnetic characteristics, also as a useful method to enhance NGF efficiency and activity, thus, paving the way for substantial neuronal repair therapeutics. © 2015 The Royal Society of Chemistry. Source


Marcus M.,Bar - Ilan University | Marcus M.,Bar Ilan Institute of Nanotechnologies and Advanced Materials | Karni M.,Bar - Ilan University | Karni M.,Bar Ilan Institute of Nanotechnologies and Advanced Materials | And 10 more authors.
Journal of Nanobiotechnology | Year: 2016

Background: The ability to direct and manipulate neuronal cells has important potential in therapeutics and neural network studies. An emerging approach for remotely guiding cells is by incorporating magnetic nanoparticles (MNPs) into cells and transferring the cells into magnetic sensitive units. Recent developments offer exciting possibilities of magnetic manipulations of MNPs-loaded cells by external magnetic fields. In the present study, we evaluated and characterized uptake properties for optimal loading of cells by MNPs. We examined the interactions between MNPs of different cores and coatings, with primary neurons and neuron-like cells. Results: We found that uncoated-maghemite iron oxide nanoparticles maximally interact and penetrate into cells with no cytotoxic effect. We observed that the cellular uptake of the MNPs depends on the time of incubation and the concentration of nanoparticles in the medium. The morphology patterns of the neuronal cells were not affected by MNPs uptake and neurons remained electrically active. We theoretically modeled magnetic fluxes and demonstrated experimentally the response of MNP-loaded cells to the magnetic fields affecting cell motility. Furthermore, we successfully directed neurite growth orientation along regeneration. Conclusions: Applying mechanical forces via magnetic mediators is a useful approach for biomedical applications. We have examined several types of MNPs and studied the uptake behavior optimized for magnetic neuronal manipulations. © 2016 The Author(s). Source

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