Nanodiamond and nanoplatinum liquid, DPV576, activates human monocyte-derived dendritic cells in vitro.
ABSTRACT The influence of nanoparticles on the immune system is poorly understood. It was recently shown that exposure to a mixture of nanodiamond (ND)- and nanoplatinum (NP)-coated material (DPV576-C) activates murine T-cells. This study examined the role of a dispersed aqueous mixture of ND/NP (DPV576) in activating human dendritic cells (DCs) in vitro.
Human monocyte-derived DCs were treated with DPV576 at various concentrations (50, 100 and 200 μg/ml) for 24 hours in vitro. Activation of DCs was determined by assessing the expression of co-stimulatory and maturation markers (CD80, CD83, CD86, HLADR), production of cytokines, and induction of proliferation of naïve CD4 T-cells. Expression of co-stimulatory molecules and cell proliferation were analysed by flow cytometry and cytokine secretion by ELISA.
DPV576 treatment of DCs resulted in: (i) increased CD83 and CD86 expression on DCs, (ii) up-regulation in the levels of DC-secreted cytokines IL-6, TNF and IL-10, and (iii) increased ability to induce proliferation in CD4(+) T-cells which is associated with increased expression of T-cell activation marker CD25.
Solution containing ND/NP (DPV576) activated human DCs and DCs-driven CD4 naive T-cell proliferation in vitro, which may be useful in boosting immune responses in cancer treatment.
- SourceAvailable from: Alia Ghoneum[Show abstract] [Hide abstract]
ABSTRACT: Nanoparticles have recently gained increased attention as drug delivery systems for the treatment of cancer due to their minute size and unique chemical properties. However, very few studies have tested the biophysical changes associated with nanoparticles on metastatic cancer cells at the cellular and sub-cellular scales. Here, we investigated the mechanical and morphological properties of cancer cells by measuring the changes in cell Young's Modulus using AFM, filopodial retraction (FR) by time lapse optical light microscopy imaging and filopodial disorganization by high resolution AFM imaging of cells upon treatment with nanoparticles. In the current study, nanomechanical changes in live murine metastatic breast cancer cells (4T1) post exposure to a nanodiamond/nanoplatinum mixture dispersed in aqueous solution (DPV576), were monitored. Results showed a decrease in Young's modulus at two hours post treatment with DPV576 in a dose dependent manner. Partial FR at 20 min and complete FR at 40 min were observed. Moreover, analysis of the retraction distance (in microns) measured over time (minutes), showed that a DPV576 concentration of 15%v/v yielded the highest FR rate. In addition, DPV576 treated cells showed early signs of filopodial disorganization and disintegration. This study demonstrates the changes in cell stiffness and tracks early structural alterations of metastatic breast cancer cells post treatment with DPV576, which may have important implications in the role of nanodiamond/nanoplatinum based cancer cell therapy and sensitization to chemotherapy drugs.Nanotechnology 10/2014; · 3.67 Impact Factor
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ABSTRACT: Recently nanoparticles have been extensively studied and have proven to be a promising candidate for cancer treatment and diagnosis. In the current study, we examined the chemo-sensitizing activity of a mixture of nanodiamond (ND) and nanoplatinum (NP) solution known as DPV576, against multidrug-resistant (MDR) human myeloid leukemia (HL60/AR) and MDR-sensitive cells (HL60). Cancer cells were cultured with different concentrations of daunorubicin (DNR) (1 × 10 (-9)-1 × 10 (-6) M) in the presence of selected concentrations of DPV576 (2.5%-10% v/v). Cancer cell survival was determined by MTT assay, drug accumulation by flow cytometry and confocal laser scanning microscopy (CLSM), and holes and structural changes by atomic force microscopy (AFM). Co-treatment of HL60/AR cells with DNR plus DPV576 resulted in the reduction of the IC50 to 1/4th. This was associated with increased incidences of holes inside the cells as compared with control untreated cells. On the other hand, HL60 cells did not show changes in their drug accumulation post-treatment with DPV576 and DNR. We conclude that DPV576 is an effective chemo-sensitizer as indicated by the reversal of HL60/AR cells to DNR and may represent a potential novel adjuvant for the treatment of chemo-resistant human myeloid leukemia.International Journal of Nanomedicine 01/2013; 8:2567-73. · 4.20 Impact Factor
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ABSTRACT: Nanoscale objects, whether of biologic origin or synthetically created, are being developed into devices for a variety of bionanotechnology diagnostic and pharmaceutical applications. However, the potential immunotoxicity of these nanomaterials and mechanisms by which they may induce adverse reactions have not received sufficient attention. Nanomaterials, depending on their characteristics and compositions, can interact with the immune system in several ways and either enhance or suppress immune system function. Cytokines perform pleiotropic functions to mediate and regulate the immune response and are generally recognized as biomarkers of immunotoxicity. While the specificity and validity of certain cytokines as markers of adverse immune response has been established for chemicals, small and macromolecular drugs, research on their applicability for predicting and monitoring the immunotoxicity of engineered nanomaterials is still ongoing. The goal of this review is to provide guidelines as to important cytokines that can be utilized for evaluating the immunotoxicity of nanomaterials and to highlight the role of those cytokines in mediating adverse reactions, which is of particular importance for the clinical development of nanopharmaceuticals and other nanotechnology-based products. Importantly, the rational design of nanomaterials of low immunotoxicity will be discussed, focusing on synthetic nanodevices, with emphasis on both the nanoparticle-forming materials and the embedded cargoes.Chemical Society Reviews 04/2013; · 30.43 Impact Factor