Search

Because mass-produced carbon nanotubes (CNTs) are strongly aggregated and highly hydrophobic, processes to make them water soluble are required for biological applications. Suspensions in surfactant solutions are often employed. Among these, Pluronic F127 appear to be highly biocompatible if used at low concentrations. Starting from these results, this work involves a systematic study to clarify the dispersion behaviour of CNTs in Pluronic F127. The results suggest a two-step process: first, the bundles disaggregate, kinetically driven by the energy supplied to the system; second, they disperse (surfactant adsorption), thermodynamically driven by the surfactant concentration. The dispersion reaction data are well fitted by a first-order kinetics reaction. By performing a pretreatment step, consisting of stirring at 70°C, the achieved concentration of CNTs in solution is twice that of the traditional process. The proposed procedure provides an optimal compromise between a low Pluronic concentration and a high CNT concentration. [ABSTRACT FROM AUTHOR]

Plasmonic nanoparticles are increasingly employed in several fields, thanks to their unique, promising properties. In particular, these particles exhibit a surface plasmon resonance combined with outstanding absorption and scattering properties. They are also easy to synthesize and functionalize, making them ideal for nanotechnology applications. However, the physicochemical properties of these nanoparticles can make them potentially toxic, even if their bulk metallic forms are almost inert. In this review, we aim to provide a more comprehensive understanding of the potential adverse effects of plasmonic nanoparticles in zebrafish (Danio rerio) during both development and adulthood, focusing our attention on the most common materials used, i.e., gold and silver. [ABSTRACT FROM AUTHOR]

Abstract: Nanoparticles engineered for biomedical applications are meant to be in contact with protein-rich physiological fluids. These proteins are usually adsorbed onto the nanoparticle's surface, forming a swaddling layer that has been described as a ‘protein corona’, the nature of which is expected to influence not only the physicochemical properties of the particles but also the internalization into a given cell type. We have investigated the process of protein adsorption onto different magnetic nanoparticles (MNPs) when immersed in cell culture medium, and how these changes affect the cellular uptake. The role of the MNPs surface charge has been assessed by synthesizing two colloids with the same hydrodynamic size and opposite surface charge: magnetite (Fe3O4) cores of 25–30 nm were in situ functionalized with (a) positive polyethyleneimine (PEI-MNPs) and (b) negative poly(acrylic acid) (PAA-MNPs). After few minutes of incubation in cell culture medium the wrapping of the MNPs by protein adsorption resulted in a 5-fold increase of the hydrodynamic size. After 24 h of incubation large MNP-protein aggregates with hydrodynamic sizes of ≈1500 nm (PAA-MNPs) and ≈3000 nm (PEI-MNPs) were observed, each one containing an estimated number of magnetic cores between 450 and 1000. These results are consistent with the formation of large protein-MNPs aggregate units having a ‘plum pudding’ structure of MNPs embedded into a protein network that results in a negative surface charge, irrespective of the MNP-core charge. In spite of the similar negative ζ-potential for both MNPs within cell culture, we demonstrated that PEI-MNPs are incorporated in much larger amounts than the PAA-MNPs units. Quantitative analysis showed that SH-SY5Y cells can incorporate 100% of the added PEI-MNPs up to ≈100 pg/cell, whereas for PAA-MNPs the uptake was less than 50%. The final cellular distribution showed also notable differences regarding partial attachment to the cell membrane. These results highlight the need to characterize the final properties of MNPs after protein adsorption in biological media, and demonstrate the impact of these properties on the internalization mechanisms in neural cells. [Copyright &y& Elsevier]

Background: The response to chemotherapy treatment of patients with pancreatic ductal adenocarcinoma (PDAC) is difficult to predict and the identification of patients who most likely will benefit from aggressive chemotherapy approaches is crucial. The concept of personalized medicine has emerged in the last years with the objective to tailor the medical treatment to the individual characteristics of each patient, and particularly to the tumor biology of each patient. The need for in-vivo xenotransplantation models for cancer patients has increased exponentially, and for this reason zebrafish avatars have gained popularity. Preliminary studies were conducted also with PDAC tissue., Aim: To develop a simple, not expensive, diffusible zebrafish embryo model as avatar for patients affected by PDAC., Methods: Tumor tissue was taken from the surgical specimen by the histopathologist. After its fragmentation into small pieces, they are stained with CM-Dil. Small pieces of stained tissue were transplanted into the yolk of wt AB zebrafish embryos with a glass capillary needle. Embryos were incubated at 35 °C in E3 medium supplemented with 1% Pen/Strep in the presence or absence of drugs for the following days in respect of the treatment plan (Gemcitabine; Gemcitabine and Oxaliplatin; Gemcitabine and nab-Paclitaxel; 5-Fluorouracil and Folinic acid and Oxaliplatin and Irinotecan). The response of zebrafish xenografts to the chemotherapy options has been analyzed by monitoring the fluorescent stained area at 2 h post injection (hpi), 1 d and 2 d post injection (dpi). In each time point, the mean size of the stained area was measured by ImageJ and it was normalized with respect to the 1 dpi time point mean relative tumor area (RTA). We evaluated the effect of the chemotherapy exposition comparing the mean RTA of each treated subgroup and the control group and evaluating the percentage reduction of the mean RTA by comparing each treated subgroup with the control group., Results: Between July 2018 and October 2019, a total of 15 patients with pancreatic cancer were prospectively enrolled. In all cases, it was possible to take a fragment of the tumor from the surgical specimen for the xenotransplantation in the zebrafish embryos. The histological examination confirmed the presence of a PDAC in all cases. In absence of chemotherapy (control group), over time the Dil-stained area showed a statistically significant increase in all cases. A statistically significant reduction of the mean RTA in the treated subgroups for at least one chemotherapy scheme was reported in 6/15 (40%) cases. The analysis of the percentage reduction of the RTA in treated subgroups in comparison to the control group revealed the presence of a linear relationship in each subgroup between the percentage reduction of the RTA and the number of cases reporting each percentage threshold considered for the analysis., Conclusion: Our model seems to be effective for the xenotransplantation of PDAC tissue and evaluation of the effect of each chemotherapy scheme on the xenotransplanted tumor tissue., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

We report a one-step synthesis protocol for obtaining polymer-coated magnetic nanoparticles (MNPs) engineered for uploading neural cells. Polyethyleneimine-coated Fe 3 O 4 nanoparticles (PEI-MNPs) with sizes of 25 ± 5 nm were prepared by oxidation of Fe(OH) 2 by nitrate in basic aqueous media and adding PEI in situ during synthesis. The obtained PEI-MNP cores displayed a neat octahedral morphology and high crystallinity. The resulting nanoparticles were coated with a thin polymer layer of about 0.7-0.9 nm, and displayed a saturation magnetization value M S = 58 A m 2 kg -1 at 250 K (64 A m 2 kg -1 for T = 10 K). Cell uptake experiments on a neuroblastoma-derived SH-SY5Y cell line were undertaken over a wide time and MNP concentration range. The results showed a small decrease in cell viability for 24 h incubation (down to 70% viability for 100 μg ml -1 ), increasing the toxic effects with incubation time (30% cell survival at 100 μg ml -1 for 7 days of incubation). On the other hand, primary neuronal cells displayed higher sensitivity to PEI-MNPs, with a cell viability reduction of 44% of the control cells after 3 days of incubation with 50 μg ml -1 . The amount of PEI-MNPs uploaded by SH-SY5Y cells was found to have a linear dependence on concentration. The intracellular distribution of the PEI-MNPs analyzed at the single-cell level by the dual-beam (FIB/SEM) technique revealed the coexistence of both fully incorporated PEI-MNPs and partially internalized PEI-MNP-clusters crossing the cell membrane. The resulting MNP-cluster distributions open the possibility of using these PEI-MNPs for magnetically driven axonal re-growth in neural 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.

The explosive growth of nanotechnology in the last years has led to dramatic innovations in pharmacology, and it is revolutioning the development of biologically active compounds. Carbon nanotubes (CNTs) are widely explored for biomedical applications such as intracellular transporters for (bio)molecules, and represent promising future tools for efficient and safe cell therapy. Due to their nanoscale dimensions, the ability to interact with cells, and their easy functionalization, CNTs are close-to-ideal vectors for an efficient and safe cell therapy, obviating the risks associated with the use of viral vectors. Notwithstanding, conflicting data concerning the biocompatibility of CNTs have been reported in the literature; while some studies point toward very low toxicity of CNTs both in vitro and in vivo, others reveal various toxic effects such as oxidative stress, DNA damage, and cell apoptosis. Thus, standardized methods and independent test systems are urgently needed to verify cytotoxicity data in this research field. In this chapter, we summarize the used methods and the achieved main results in our laboratories concerning multiwalled carbon nanotubes (MWCNTs) biocompatibility studies. The in vitro response of human neuroblastoma cell line and primary mouse neurons was investigated following the exposure to different samples of MWCNTs in order to evaluate their effects on cell viability, oxidative stress, and apoptosis. Moreover, in vivo neurocompatibility tests were carried out through injections in mouse brains.

Carbon nanotubes are widely used for biomedical applications as intracellular transporters of biomolecules, due to their high propensity to cross cell membranes. In this review we summarize the recent advancement in the functionalization of carbon nanotubes, focusing particular attention on the chemistry involved in the preparation of nanovectors for drug delivery systems, and on the physical and chemical properties that affect cellular up-take and biodistribution phenomena.