Overview of Cell Death Mechanisms Induced by Rose Bengal Acetate-Photodynamic Therapy

Photodynamic Therapy (PDT) is a non-invasive treatment for different pathologies, cancer included, using three key components: non-toxic light-activated drug (Photosensitizer, PS), visible light, and oxygen. Their interaction triggers photochemical reactions leading to Reactive Oxygen Species (ROS) generation, that mediate cytotoxicity and cell death. In the present paper, the most important findings about the synthetic dye Rose Bengal Acetate (RBAc), an emerging photosensitizer for its efficient induction of cell death, will be reported with the aim to integrate RBAc phototoxicity to novel therapeutic PDT strategies against tumour cells. After its perinuclear intracellular localization, RBAc causes multiple subcellular organelles damage, that is, mitochondria, Endoplasmic Reticulum (ER), lysosomes, and Golgi complex. Indeed, RBAc exerts long-term phototoxicity through activation of both caspase-independent and- dependent apoptotic pathways and autophagic cell death. In particular, this latter cell death type may promote cell demise when apoptotic machinery is defective. The deep knowledge of RBAc photocytotoxicity will allow to better understand its potential photomedicine application in cancer

Synthesis and in vitro cytotoxicity of glycans-capped silver nanoparticles

Silver nanostructures were successfully synthesized through a simple and "green" method using saccharides as reducing and caping agent. Transmission electron microscopy (TEM) and UV-Vis absorption were used to certify the quality of the silver nanoparticles obtained: firstly, size and dispersion. In this work Silver NanoParticles (AgNPs) cytotoxicity related to saccharides capping (Glucose and (GlucoseSucrose) was explored in human epithelia cervix carcinoma cells (HeLa). The cells were incubated with increasing AgNPs number/cell and HeLa cells viability was monitored for a period of 48 h compared with the positive and negative controls. We observed that the toxicity increases with incubation time and with AgNPs number/cell. In particular, the different cytotoxic degree of the AgNPs, i.e. AgNP-G are more toxic than AgNP-GS, suggest that the cytotoxic effects are largely depended on the capping agent. The highest concentration of AgNP-G number/cell is able to induce extensive cell death of HeLa cells soon after 1hr of incubation; conversely the lowest concentration of AgNP-GS number/cell, surprisingly, is able to induce cell proliferation

Looking to the Future of the Role of Macrophages and Extracellular Vesicles in Neuroinflammation in ALS

Neuroinflammation is a common pathological feature of amyotrophic lateral sclerosis (ALS). Although scientific evidence to date does not allow defining neuroinflammation as an ALS trigger, its role in exacerbating motor neuron (MNs) degeneration and disease progression is attracting research interest. Activated CNS (Central Nervous System) glial cells, proinflammatory peripheral and infiltrated T lymphocytes and monocytes/macrophages, as well as the immunoreactive molecules they release, represent the active players for the role of immune dysregulation enhancing neuroinflammation. The crosstalk between the peripheral and CNS immune cells significantly correlates with the survival of ALS patients since the modification of peripheral macrophages can downregulate inflammation at the periphery along the nerves and in the CNS. As putative vehicles for misfolded protein and inflammatory mediators between cells, extracellular vesicles (EVs) have also drawn particular attention in the field of ALS. Both CNS and peripheral immune cells release EVs, which are able to modulate the behavior of neighboring recipient cells; unfortunately, the mechanisms involved in EVs-mediated communication in neuroinflammation remain unclear. This review aims to synthesize the current literature regarding EV-mediated cell-to-cell communication in the brain under ALS, with a particular point of view on the role of peripheral macrophages in responding to inflammation to understand the biological process and exploit it for ALS management

Molecular Characterization of Temozolomide-Treated and Non Temozolomide-Treated Glioblastoma Cells Released Extracellular Vesicles and Their Role in the Macrophage Response

Extracellular vesicles (EVs) are widely investigated in glioblastoma multiforme (GBM) for their involvement in regulating GBM pathobiology as well as for their use as potential biomarkers. EVs, through cell-to-cell communication, can deliver proteins, nucleic acids, and lipids that are able to reprogram tumor-associated macrophages (TAMs). This research is aimed to concentrate, characterize, and identify molecular markers of EVs subtypes released by temozolomide (TMZ)-treated and non TMZ-treated four diverse GBM cells. Morphology, size distribution, and quantity of small (sEVs) and large (lEVs) vesicles were analyzed by cryo-TEM. Quality and quantity of EVs surface markers were evaluated, having been obtained by Western blotting. GBM cells shed a large amount of EVs, showing a cell line dependent molecular profile A comparative analysis distinguished sEVs and lEVs released by temozolomide (TMZ)-treated and non TMZ-treated GBM cells on the basis of quantity, size and markers expression. Finally, the GBM-derived sEVs and lEVs, irrespective of TMZ treatment, when challenged with macrophages, modulated cell activation toward a tendentially M2b-like phenotype

Microscopies at the nanoscale for nano-scale drug delivery systems

One of the frontier of nanoscience is undoubtedly represented by the use of nanotechnologies in the pharmaceutical research. During the last decades a big family of nanostructures that have a surface-acting action, such as NanoParticles (NPs), lipid nanocarriers and many more, have been developed to be used as Drug Delivery Systems (DDSs). However, these nanocarriers opened also new frontiers in nanometrology, requiring an accurate morphological characterization, near atomic resolution, before they are really available to clinicians to ascertain their elemental composition, to exclude the presence of contaminants introduced during the synthesis procedure and to ensure biocompatibility. Classical Transmission (TEM) and Scanning Electron Microscopy (SEM) techniques frequently have to be adapted for an accurate analysis of formulation morphology, especially in case of hydrated colloidal systems. Specific techniques such as environmental scanning microscopy and/or cryo preparation are required for their investigation. Analytical Electron Microscopy (AEM) techniques such as Electron Energy-Loss Spectroscopy (EELS) or Energy-Dispersive X-ray Spectroscopy (EDXS) are additional assets to determine the elemental composition of the systems. Here we will discuss the importance of Electron Microscopy (EM) as a reliable tool in the pharmaceutical research of the 21st century, focalizing our attention on advantages and limitations of different kind of NPs (in particular silver and carbon NPs, cubosomes) and vesicles (liposomes and niosomes)

Novel therapeutic delivery of Nanocurcumin in central nervous system related disorders

Nutraceuticals represent complementary or alternative beneficial products to the expensive and high-tech therapeutic tools in modern medicine. Nowadays, their medical or health benefits in preventing or treating different types of diseases is widely accepted, due to fewer side effects than synthetic drugs, improved bioavailability and long half-life. Among herbal and natural compounds, curcumin is a very attractive herbal supplement considering its multipurpose properties. The potential effects of curcumin on glia cells and its therapeutic and protective properties in central nervous system (CNS)-related disorders is relevant. However, curcumin is unstable and easily degraded or metabolized into other forms posing limits to its clinical development. This is particularly important in brain pathologies determined blood brain barrier (BBB) obstacle. To enhance the stability and bioavailability of curcumin, many studies focused on the design and development of curcumin nanodelivery systems (nanoparticles, micelles, dendrimers, and diverse nanocarriers). These nanoconstructs can increase curcumin stability, solubility, in vivo uptake, bioactivity and safety. Recently, several studies have reported on a curcumin exosome-based delivery system, showing great therapeutical potential. The present work aims to review the current available data in improving bioactivity of curcumin in treatment or prevention of neurological disorders

Moderate Static Magnetic Field (6 mT)-Induced Lipid Rafts Rearrangement Increases Silver NPs Uptake in Human Lymphocytes

One of the most relevant drawbacks in medicine is the ability of drugs and/or imaging agents to reach cells. Nanotechnology opened new horizons in drug delivery, and silver nanoparticles (AgNPs) represent a promising delivery vehicle for their adjustable size and shape, high-density surface ligand attachment, etc. AgNPs cellular uptake involves different endocytosis mechanisms, including lipid raft-mediated endocytosis. Since static magnetic fields (SMFs) exposure induces plasma membrane perturbation, including the rearrangement of lipid rafts, we investigated whether SMF could increase the amount of AgNPs able to pass the peripheral blood lymphocytes (PBLs) plasma membrane. To this purpose, the effect of 6-mT SMF exposure on the redistribution of two main lipid raft components (i.e., disialoganglioside GD3, cholesterol) and on AgNPs uptake efficiency was investigated. Results showed that 6 mT SMF: (i) induces a time-dependent GD3 and cholesterol redistribution in plasma membrane lipid rafts and modulates gene expression of ATP-binding cassette transporter A1 (ABCA1), (ii) increases reactive oxygen species (ROS) production and lipid peroxidation, (iii) does not induce cell death and (iv) induces lipid rafts rearrangement, that, in turn, favors the uptake of AgNPs. Thus, it derives that SMF exposure could be exploited to enhance the internalization of NPs-loaded therapeutic or diagnostic molecules

Coherent population transfer in coupled semiconductor quantum dots

We propose a solid-state implementation of stimulated Raman adiabatic passage in two coupled semiconductor quantum dots. Proper combination of two pulsed laser fields allows the coherent carrier transfer between the two nanostructures without suffering significant losses due to environment coupling. By use of a general solution scheme for the carrier states in the double-dot structure, we identify the pertinent dot and laser parameters.Comment: 4 pages, accepted for publication in Applied Physics Letter

High ordered biomineralization induced by carbon nanoparticles in the sea urchin Paracentrotus lividus

A surprising and unexpected biomineralization process was observed during toxicological assessment of carbon nanoparticles on Paracentrotus lividus (sea urchin) pluteus larvae. The larvae activate a process of defense against external material, by incorporating the nanoparticles into microstructures of aragonite similarly to pearl oysters. Aiming at a better understanding of this phenomenon, the larvae were exposed to increasing concentrations of carbon nanoparticles and the biomineralization products were analyzed by electron microscopy, x-ray diffraction and Raman spectroscopy. In order to evaluate the possible influence of Sp-CyP-1 expression on this biomineralization process by larvae, analyses of gene expression (Sp-CyP-1) and calcein labeling were performed. Overall, we report experimental evidence about the capability of carbon nanoparticles to induce an increment of Sp-CyP-1 expression with the consequent activation of a biomineralization process leading to the production of a new pearl-like biomaterial never previously observed in sea urchins