Force: A messenger of axon outgrowth

The axon is a sophisticated macromolecular machine composed of interrelated parts that transmit signals like spur gears transfer motion between parallel shafts. The growth cone is a fine sensor that integrates mechanical and chemical cues and transduces these signals through the generation of a traction force that pushes the tip and pulls the axon shaft forward. The axon shaft, in turn, senses this pulling force and transduces this signal in an orchestrated response, coordinating cytoskeleton remodeling and intercalated mass addition to sustain and support the advancing of the tip. Extensive research suggests that the direct application of active force is per se a powerful inducer of axon growth, potentially bypassing the contribution of the growth cone. This review provides a critical perspective on current knowledge of how the force is a messenger of axon growth and its mode of action for controlling navigation, including aspects that remain unclear. It also focuses on novel approaches and tools designed to mechanically manipulate axons, and discusses their implications in terms of potential novel therapies for re-wiring the nervous system

Superparamagnetic Nanoparticles: A Biodistribution Study Using Xenopus laevis Embryos

Various in-vivo biological models have been proposed for studying the interactions of nanomaterials with biological systems. Recently, there has been a significant increase in interest in the use of non-mammalian embryos, such as the frog Xenopus laevis as valid models for research in nanomedicine. In the present work, we demonstrate that X. laevis is a powerful model for the study of the biodistribution of superparamagnetic nanoparticles (SPION), extensively used in biomedical field for cell separation, MRI diagnostics and magnetic drug-targeting. 10 nl of 25 mg/ml of SPIONs (nano-screen MAG/ARA 200 nm, Chemicell) were microinjected. The biodistribution of SPIONs, following cardiac or pronephros injection of anesthetized frog larvae at stage 37, was studied by both in-vivo florescence and by Prussian blue staining of paraffin sections of the larvae after 24, 48, 72 or 96 hours (at 14 °C). The study confirmed that SPIONs diffused from either injection site by blood stream to all larval organs, being still present after 96 hours of injection

Nano-oncology: clinical application for cancer therapy and future perspectives

Nano-oncology, the application of Nanomedicine to cancer diagnosis and treatment, has the potential to transform clinical oncology by enhancing the efficacy of cancer chemotherapy for a wide spectrum of invasive cancers. It achieves this by enabling novel drug delivery systems which target the tumour site with several functional molecules, including tumour-specific ligands, antibodies, cytotoxic agents, and imaging probes simultaneously thereby improving tumour response rates in addition to significant reduction of the systemic toxicity associated with current chemotherapy regimens. For this reason, nano-oncology is attracting considerable scientific interest and a growing investment by the global pharmaceutical industry. Several therapeutic nano-carriers have been approved for clinical use and others are undergoing phase II and III clinical trials. This paper describes the current approved formulations, such as liposomes and polymeric nanoparticles, and discusses the overall present status of nano-oncology as an emerging branch of nanomedicine and its future perspectives in cancer and therapy

Zinc oxide nanoparticles as selective killers of proliferating cells

Background: It has recently been demonstrated that zinc oxide nanoparticles (ZnO NPs) induce death of cancerous cells whilst having no cytotoxic effect on normal cells. However, there are several issues which need to be resolved before translation of zinc oxide nanoparticles into medical use, including lack of suitable biocompatible dispersion protocols and a better understanding being needed of the mechanism of their selective cytotoxic action. Methods: Nanoparticle dose affecting cell viability was evaluated in a model of proliferating cells both experimentally and mathematically. The key issue of selective toxicity of ZnO NPs toward proliferating cells was addressed by experiments using a biological model of noncancerous cells, ie, mesenchymal stem cells before and after cell differentiation to the osteogenic lineage. Results: In this paper, we report a biocompatible protocol for preparation of stable aqueous solutions of monodispersed zinc oxide nanoparticles. We found that the threshold of intracellular ZnO NP concentration required to induce cell death in proliferating cells is 0.4 ± 0.02 mM. Finally, flow cytometry analysis revealed that the threshold dose of zinc oxide nanoparticles was lethal to proliferating pluripotent mesenchymal stem cells but exhibited negligible cytotoxic effects to osteogenically differentiated mesenchymal stem cells. Conclusion: Results confirm the ZnO NP selective cytotoxic action on rapidly proliferating cells, whether benign or malignant

pdzrn3 is required for pronephros morphogenesis in Xenopus laevis

Pdzrn3, a multidomain protein with E3-ubiquitin ligase activity, has been reported to play a role in myoblast and osteoblast differentiation and, more recently, in neuronal and endothelial cell development. The expression of the pdzrn3 gene is developmentally regulated in various vertebrate tissues, including muscular, neural and vascular system. Little is known about its expression during kidney development, although genetic polymorphisms and alterations around the human pdzrn3 chromosomal region have been found to be associated with renal cell carcinomas and other kidney diseases. We investigated the pdzrn3 spatio-temporal expression pattern in Xenopus laevis embryos by in situ hybridization. We focused our study on the development of the pronephros, which is the embryonic amphibian kidney, functionally similar to the most primitive nephric structures of human kidney. To explore the role of pdzrn3 during renal morphogenesis, we performed loss-of-function experiments, through antisense morpholino injections and analysed the morphants using specific pronephric markers. Dynamic pdzrn3 expression was observed in embryonic tissues, such as somites, brain, eye, blood islands, heart, liver and pronephros. Loss of function experiments resulted in specific alterations of pronephros development. In particular, at early stages, pdzrn3 depletion was associated with a reduction of the pronephros anlagen and later, with perturbations of the tubulogenesis, including deformation of the proximal tubules. Rescue experiments, in which mRNA of the zebrafish pdzrn3 orthologue was injected together with the morpholino, allowed recovery of the kidney phenotypes. These results underline the importance of pdzrn3 expression for correct nephrogenesis

Magnetic nanoparticles: a strategy to target the choroidal layer in the posterior segment of the eye

Despite the higher rate of blindness due to population aging, minimally invasive and selective drug delivery to the eye still remains an open challenge, especially in the posterior segment. The retina, the retinal pigment epithelium (RPE) and the choroid are posterior segment cell layers, which may be affected by several diseases. In particular, damages to the choroid are associated with poor prognosis in the most severe pathologies. A drug delivery approach, able to target the choroid, is still missing. Recently, we demonstrated that intravitreally injected magnetic nanoparticles (MNP) are able to rapidly and persistently localise within the RPE in an autonomous manner. In this work we functionalised the MNP surface with the vascular endothelial growth factor, a bioactive molecule capable of transcytosis from the RPE towards more posterior layers. Such functionalisation successfully addressed the MNPs to the choroid, while MNP functionalised with a control polypeptide (poly-L-lysine) showed the same localisation pattern of the naked MNP particles. These data suggest that the combination of MNP with different bioactive molecules could represent a powerful strategy for cell-specific targeting of the eye posterior segment

A microfabricated physical sensor for atmospheric mercury monitoring

Abstract A new microfabricated physical sensor for elemental gaseous mercury (Hg 0 ) determinations has been developed and experimentally tested by the authors. Hg 0 represents 90-99% of atmospheric mercury forms. The sensor is based on the technique of resistivity variation of thin gold film, characterised by high selectivity and absence of optical parts. The sensor consists of four identical thin gold film resistors mounted in Wheatstone bridge configuration. Two resistors work as sensitive elements and the others as reference, in order to minimise the influence of temperature variation. The absorption of Hg 0 on the gold film produces a change in the resistivity of the amalgam. Far from the saturation, this change is proportional to the amount of the absorbed Hg 0 . The adsorption behaviour of the sensor deposited by sputtering on two different substrates (glass and Printed Circuit Board (PCB)) have been investigated. The sensors showed to work in a large range of linearity and need a low power during the regeneration process. Sensors on glass and PCB substrates underwent numerous regeneration cycles without inflicting any mechanical or electrical damages to the resistors. The presented experimental results describe the features of both sensors pointing out advantages and drawbacks of the used substrates. The PCB substrate seems to have more suitable characteristics for developing a new mercury 'smart' sensor

In Vivo Recognition of Human Vascular Endothelial Growth Factor by Molecularly Imprinted Polymers

One of the mechanisms responsible for cancer-induced increased blood supply in malignant neoplasms is the overexpression of vascular endothelial growth factor (VEGF). Several antibodies for VEGF targeting have been produced for both imaging and therapy. Molecularly imprinted polymer nanoparticles, nanoMIPs, however, offer significant advantages over antibodies, in particular in relation to improved stability, speed of design, cost and control over functionalization. In the present study, the successful production of nanoMIPs against human VEGF is reported for the first time. NanoMIPs were coupled with quantum dots (QDs) for cancer imaging. The composite nanoparticles exhibited specific homing toward human melanoma cell xenografts, overexpressing hVEGF, in zebrafish embryos. No evidence of this accumulation was observed in control organisms. These results indicate that nanoMIPs are promising materials which can be considered for advancing molecular oncological research, in particular when antibodies are less desirable due to their immunogenicity or long production time

Phantoms in medicine: the case of ophthalmology

Physical and in-silico phantoms have revealed extremely useful in the development of new surgical techniques and medical devices and for training purposes. The fabrication of eye phantoms requires knowledge of anatomy and physical principles beyond the eye physiology and medical instruments used in the clinical scenario. After a proper definition of phantoms and the discussion about their classification, the present work reviews the various phantoms developed in ophthalmology, illustrating the rationale of their design