Production of Living Nanoparticles for Blood Cancer Therapy

Current cancer therapies leave much to be desired because they are very harmful to the patient and cause a significant decrease in quality of life. Chimeric Antigen Receptors (CAR) are a promising novel approach for treating specific types of leukemia due to their binding affinity for proteins expressed solely on leukemia B cells. This approach increases specificity of how cells receive treatment, thus allowing for the destruction of cancerous cells while leaving the healthy cells unharmed. In this experiment, we show that production of CAR expressing exosomes (liposome like vesicles produced naturally by human cells) is possible through cell transfection. This finding demonstrates that a new wave of cancer therapeutics, that are more specific and have less harmful side effects, are producible

Evaluation of engineered nanoparticle toxic effect on wastewater microorganisms: current status and challenges

The use of engineered nanoparticles (ENPs) in a wide range of products is associated with an increased concern for environmental safety due to their potential toxicological and adverse effects. ENPs exert antimicrobial properties through different mechanisms such as the formation of reactive oxygen species, disruption of physiological and metabolic processes. Although there are little empirical evidences on environmental fate and transport of ENPs, biosolids in wastewater most likely would be a sink for ENPs. However, there are still many uncertainties in relation to ENPs impact on the biological processes during wastewater treatment. This review provides an overview of the available data on the plausible effects of ENPs on AS and AD processes, two key biologically relevant environments for understanding ENPs–microbial interactions. It indicates that the impact of ENPs is not fully understood and few evidences suggest that ENPs could augment microbial-mediated processes such as AS and AD. Further to this, wastewater components can enhance or attenuate ENPs effects. Meanwhile it is still difficult to determine effective doses and establish toxicological guidelines, which is in part due to variable wastewater composition and inadequacy of current analytical procedures. Challenges associated with toxicity evaluation and data interpretation highlight areas in need for further research studies

Iron-based ferritin nanocore as a contrast agent

Self-assembling protein cages have been exploited as templates for nanoparticle synthesis. The ferritin molecule, a protein cage present in most living systems, stores excess soluble ferrous iron in the form of an insoluble ferric complex within its cavity. Magnetic nanocores formed by loading excess iron within an engineered ferritin from Archaeoglobus fulgidus (AfFtn-AA) were studied as a potential magnetic resonance (MR) imaging contrast agent. The self-assembly characteristics of the AfFtn-AA were investigated using dynamic light scattering technique and size exclusion chromatography. Homogeneous size distribution of the assembled nanoparticles was observed using transmission electron microscopy. The magnetic properties of iron-loaded AfFtn-AA were studied using vibrating sample magnetometry. Images obtained from a 3.0 T whole-body MRI scanner showed significant brightening of T1 images and signal loss of T2 images with increased concentrations of iron-loaded AfFtn-AA. The analysis of the MR image intensities showed extremely high R2 values (5300 mM^(−1) s^(−1)) for the iron-loaded AfFtn-AA confirming its potential as a T2 contrast agent

Nanomedicine for the Treatment of Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma, or NHL, is the predominant category of lymphoma. NHL is a type of lymphoid hematopoietic malignancy which approximately 70,000 Americans are diagnosed with annually, with the number of diagnoses growing annually. For decades, chemotherapy was the standard treatment of care, but since the discovery in 1997, monoclonal antibodies are increasingly used as an alternate form of therapy. Nonetheless, almost 20,000 Americans succumb to NHL annually, which highlights the translational gap between preclinical research and the market. Although a lot of progress has been made in therapy options by immunotherapy and combination chemotherapy, the ingenuity of nanomedicine may bridge the translational difficulties while serving as a novel form of therapy capable of eradicating solid tumors. The versatility of nanoparticles allows for personalized approach to NHL, as opposed to generalized medicine, since the subtypes of lymphoma are pathologically very different from one another

Current Approaches of Occupational and Safety Health Management in Work Environments Containing Nanoparticles

The development of nanotechnology is particularly in recent years very dynamic and is applied in many not only technical branches. This is not possible to say about monitoring of possible health and environmental undesirable influence. The first area of possible risk assessment is work environment because there is a lot of possible ways to exposition. The aim of the paper is to analyze current situation in the field of occupational safety and health management in the workspace with occurrence of nanoparticles not only like the engineered nanomaterials. Because there is a lot of influence which could have the negative impact on the employee's healt

Nanoparticles and cars : analysis of potential sources

Urban health is potentially affected by particle emissions. The potential toxicity of nanoparticles is heavily debated and there is an enormous global increase in research activity in this field. In this respect, it is commonly accepted that nanoparticles may also be generated in processes occurring while driving vehicles. So far, a variety of studies addressed traffic-related particulate matter emissions, but only few studies focused on potential nanoparticles. Therefore, the present study analyzed the literature with regard to nanoparticles and cars. It can be stated that, to date, only a limited amount of research has been conducted in this area and more studies are needed to 1) address kind and sources of nanoparticles within automobiles and to 2) analyse whether there are health effects caused by these nanoparticles

Engineered ferritin for lanthanide binding

Ferritin H-homopolymers have been extensively used as nanocarriers for diverse applications in the targeted delivery of drugs and imaging agents, due to their unique ability to bind the transferrin receptor (CD71), highly overexpressed in most tumor cells. In order to incorporate novel fluorescence imaging properties, we have fused a lanthanide binding tag (LBT) to the C-terminal end of mouse H-chain ferritin, HFt. The HFt-LBT possesses one high affinity Terbium binding site per each of the 24 subunits provided by six coordinating aminoacid side chains and a tryptophan residue in its close proximity and is thus endowed with strong FRET sensitization properties. Accordingly, the characteristic Terbium emission band at 544 nm for the HFt-LBT Tb(III) complex was detectable upon excitation of the tag enclosed at two order of magnitude higher intensity with respect to the wtHFt protein. X-ray data at 2.9 Å and cryo-EM at 7 Å resolution demonstrated that HFt-LBT is correctly assembled as a 24-mer both in crystal and in solution. On the basis of the intrinsic Tb(III) binding properties of the wt protein, 32 additional Tb(III) binding sites, located within the natural iron binding sites of the protein, were identified besides the 24 Tb(III) ions coordinated to the LBTs. HFt-LBT Tb(III) was demonstrated to be actively uptaken by selected tumor cell lines by confocal microscopy and FACS analysis of their FITC derivatives, although direct fluorescence from Terbium emission could not be singled out with conventional, 295–375 nm, fluorescence excitation

Photochemical transformation of perfluoroalkyl acid precursors in water using engineered nanomaterials

The production of perfluoroalkyl acids (PFAAs) has been phased out over recent decades; however, no significant decline in their environmental concentrations has been observed. This is partly due to the photochemical decomposition of PFAAs precursors (PrePFAAs) which remain in extensive use. The decomposition of PrePFAAs may be accelerated by the light-activated engineered nanomaterials (ENMs) in water. In light of this hypothesis, we investigated the photochemical transformation of three PrePFAAs, which are 8:2 fluorotelomer sulfonic acid (8:2 FTSA), 8:2 fluorotelomer alcohol (8:2 FTOH), and 2-(N-ethylperfluorooctane-1-sulfonamido ethyl] phosphate (SAmPAP), in the presence of six ENMs under simulated sunlight irradiation. The transformation rates of 8:2 FTSA and 8:2 FTOH were increased by 2–6 times when in the presence of six ENMs. However, most of ENMs appeared to inhibit the decomposition of SAmPAP. The transformation rates of PrePFAAs were found to depend on the yield of reactive oxygen species generated by ENMs, but the rates were also related to compound photo-stability, adsorption to surfaces, and photo-shielding effects. The PrePFAAs are transformed to perfluorooctanoic acid (PFOA) or/and perfluorooctane sulfonate (PFOS) with higher toxicity and longer half-life, PFOA or PFOS and a few PFAAs having shorter carbon chain lengths. Higher concentrations of the PFAAs photodegradation products were observed in the presence of most of the ENMs

In vitro toxicity of nanoceria: effect of coating and stability in biofluids

Due to the increasing use of nanometric cerium oxide in applications, concerns about the toxicity of these particles have been raised and have resulted in a large number of investigations. We report here on the interactions between 7 nm anionically charged cerium oxide particles and living mammalian cells. By a modification of the particle coating including low-molecular weight ligands and polymers, two generic behaviors are compared: particles coated with citrate ions that precipitate in biofluids and particles coated with poly(acrylic acid) that are stable and remain nanometric. We find that nanoceria covered with both coating agents are taken up by mouse fibroblasts and localized into membrane-bound compartments. However, flow cytometry and electron microscopy reveal that as a result of their precipitation, citrate-coated particles interact more strongly with cells. At cerium concentration above 1 mM, only citrate-coated nanoceria (and not particles coated with poly(acrylic acid)) display toxicity and moderate genotoxicity. The results demonstrate that the control of the surface chemistry of the particles and its ability to prevent aggregation can affect the toxicity of nanomaterials.Comment: 33 pages 10 figures, accepted at Nanotoxicolog