(4,4′-Dimethyl-2,2′-bipyridine-κ2 N,N′)(dimethyl sulfoxide-κO)diiodidozinc(II)

In the title compound, [ZnI2(C12H12N2)(C2H6OS)], the ZnII ion is coordinated by two N atoms from a 4,4′-dimethyl-2,2′-bipyridine ligand, one O atom from a dimethyl sulfoxide mol­ecule and two I atoms in a distorted trigonal-bipyramidal geometry. Intra­molecular C—H⋯O hydrogen bonds and inter­molecular π–π stacking inter­actions between the pyridine rings [centroid–centroid distances = 3.637 (4) and 3.818 (4) Å] are present in the crystal structure

Engineering of pulmonary surfactant corona on inhaled nanoparticles to operate in the lung system

Exposure of inhaled nanoparticles (NPs) to the deep lung tissue results in the adsorption of pulmonary surfactant (PSf) on the surface of NPs and the formation of a biomolecular corona. The adsorption of the peculiar phospholipids (PLs) and surfactant proteins (SPs) provides NPs with a new bio-identity, which likely changes their corresponding interactions with cells and other bio-systems. Exploring the interaction of NPs with the PSf film at the alveolar air-fluid interface can provide valuable insights into the role of biofluids in the cellular uptake of NPs and their nanotoxic effects. Wrapping biomembranes around NPs and the formation of lipoprotein corona regulate viscoelastic changes, NP insertion into the membrane, and cellular uptake of NPs. In this review, a concise overview has been presented on the engineering of PSf on inhaled NPs to operate in lung environment. First, the physiological barriers in the pulmonary delivery of NPs and approaches to regulating their pulmonary fate are introduced and rationalized. Next, a short description is given on the different sources used for exploring the interfacial performance of inhaled NPs in vitro. A discussion is then presented on SP corona formation on the surface of inhaled NPs, coronal proteome/lipidome in respiratory tract lining fluid (RTLF), regulation of NP aggregation and surfactant flow characteristics, PSf corona and its functional role in the cellular uptake of NPs, followed by explanations on the clinical correlations of PSf corona formation/inhibition on the surface of NPs. Finally, the challenges and future perspectives of the field have been discussed. This review can be harnessed to exploit PSf for the development of safe and bio-inspired pulmonary drug delivery strategies.</p

Aqua­(4,4′-dimethyl-2,2′-bipyridine-κ2 N,N′)(nitrato-κO)(nitrato-κ2 O,O′)zinc

In the title compound, [Zn(NO3)2(C12H12N2)(H2O)], the ZnII atom is six-coordinated in a distorted octa­hedral geometry by two N atoms from a chelating 4,4′-dimethyl-2,2′-bipyridine ligand, one water O atom, one O atom from a monodentate nitrate anion and two O atoms from a chelating nitrate anion. In the crystal, there are aromatic π–π contacts between the pyridine rings [centroid–centroid distances = 3.9577 (13) Å] and inter­molecular O—H⋯O and C—H⋯O hydrogen bonds

Dibromido(4,4′-dimethyl-2,2′-bipyridine-κ2 N,N′)zinc(II)

The asymmetric unit of the title compound, [ZnBr2(C12H12N2)], contains two half-mol­ecules; both are completed by crystallographic twofold axes running through the ZnII atoms which are coordinated by an N,N′-bidentate 4,4′-dimethyl-2,2′-bipyridine ligand and two Br− ions, resulting in distorted ZnN2Br2 tetra­hedral coordination geometries. In the crystal, C—H⋯Br inter­actions link the mol­ecules

Generation of natural killer cell-mimic nanoparticles to target tumour cells

Natural killer (NK) cells are effector immune cells in the innate immune system. It is increasingly recognised that NK cells play a crucial role eliminating emerging tumour cells. Some tumour cells however can escape and evolve by developing strategies to inactivate or hide from NK cells. Here, we engineered a nanoparticle (NP) able to identify and kill specific cancer cells using mechanisms NK cells utilise. The first part of the thesis presents my work on developing liposomes functionalised with the NK-expressed death ligand, TNF-related apoptosis-inducing ligand (TRAIL) enabling tumour-specific cytotoxicity. The cytotoxic potential of the TRAIL-conjugated liposomes (LP/TRAIL) was confirmed using a panel of cancer cell lines. Our results showed that LP/TRAIL had significantly higher pro-apoptotic potential than the soluble form of TRAIL (sTRAIL) showing that LPs enable delivery of TRAIL in its native-like, biologically active conformation. The second part of the thesis presents the work on improving the bioactivity of LP/TRAIL by functionalisation with tumour-targeting antibodies thus generating NK cell-mimic NPs. The anticancer efficiency of the NK cell-mimic NPs was evaluated in vitro, ex vivo and in vivo. In vitro, NK cell-mimic LPs showed slightly increased cytotoxicity than LP/TRAIL against acute myeloid leukaemia (AML) cell lines. Ex vivo studies, using primary, patient-derived AML cells corroborated the in vitro findings, where the NK cell-mimic LPs had superior cytotoxicity over sTRAIL and LP/TRAIL. Furthermore, NK cell-mimic NPs could kill patient-derived leukemic stem cells substantially more than sTRAIL or LP/TRAIL. The efficacy of the NK cell-mimic LPs was finally assessed in vivo, using a disseminated (bone marrow-localised) AML mouse model. In this study, while LP/TRAIL reduced tumour burden, NK cell-mimic NPs were markedly more effective, underlining that features of NK cells can be replicated in nanomedicine to achieve active tumour targeting linked with potent and selective killing of cancer cells

TRAIL in the Treatment of Cancer: From Soluble Cytokine to Nanosystems

The death ligand tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF cytokine superfamily, has long been recognized for its potential as a cancer therapeutic due to its low toxicity against normal cells. However, its translation into a therapeutic molecule has not been successful to date, due to its short in vivo half-life associated with insufficient tumor accumulation and resistance of tumor cells to TRAIL-induced killing. Nanotechnology has the capacity to offer solutions to these limitations. This review provides a perspective and a critical assessment of the most promising approaches to realize TRAIL’s potential as an anticancer therapeutic, including the development of fusion constructs, encapsulation, nanoparticle functionalization and tumor-targeting, and discusses the current challenges and future perspectives

Experimental investigation on thermal performance of covalently functionalized hydroxylated and non-covalently functionalized multi-walled carbon nanotubes/transformer oil nanofluid

International audienceThe study investigated the effect of adding covalently functionalized-hydroxylated multi-walled carbon nanotubes (MWCNTs-OH) and non-covalently-functionalized MWCNTs on the breakdown voltage and thermal properties of transformer oil in a rectangular chamber. The novelty of the present study is the use of covalently functionalized hydroxylated and non-covalently functionalized multi-walled carbon nanotubes in transformer oil, and the reason for the selection of these nanoparticles is the high intrinsic thermal conductivity compared to other nanoparticles. Between both studied nanofluids, the thermal and electrical performance of covalently functionalized MWCNTs-OH was better due to the highest increase in heat transfer coefficient of free transfer and using fan was related to covalently functionalized MWCNTs-OH, which increased by 26.23% and 30.08%, respectively. Also, by measuring the breakdown voltage, it was found that the MWCNTs-OH of 0.001 wt% had the lowest reduction compared to the base fluid and was equal to 55.6 kV, which showed good performance because the specified standard for transformer oil breakdown voltage property is between 30 kV and 70 kV. According to the results, covalently functionalized hydroxylated MWCNTs-OH/transformer oil nanofluid has better thermal performance than pure oil, which prevents the transformer from rising in temperature and can also be used as electrical insulation in transformers

Investigating the Interaction of Fe Nanoparticles with Lysozyme by Biophysical and Molecular Docking Studies.

Herein, the interaction of hen egg white lysozyme (HEWL) with iron nanoparticle (Fe NP) was investigated by spectroscopic and docking studies. The zeta potential analysis revealed that addition of Fe NP (6.45±1.03 mV) to HEWL (8.57±0.54 mV) can cause to greater charge distribution of nanoparticle-protein system (17.33±1.84 mV). In addition, dynamic light scattering (DLS) study revealed that addition of Fe NP (92.95±6.11 nm) to HEWL (2.68±0.37 nm) increases suspension potential of protein/nanoparticle system (51.17±3.19 nm). Fluorescence quenching studies reveled that both static and dynamic quenching mechanism occur and hydrogen bond and van der Waals interaction give rise to protein-NP system. Synchronous fluorescence spectroscopy of HEWL in the presence of Fe NP showed that the emission maximum wavelength of tryptophan (Trp) residues undergoes a red-shift. ANS fluorescence data indicated a dramatic exposure of hydrophobic residues to the solvent. The considerable reduction in melting temperature (T(m)) of HEWL after addition of Fe NP determines an unfavorable interaction system. Furthermore circular dichoroism (CD) experiments demonstrated that, the secondary structure of HEWL has not changed with increasing Fe NP concentrations; however, some conformational changes occur in tertiary structure of HEWL. Moreover, protein-ligand docking study confirmed that the Fe NP forms hydrogen bond contacts with HEWL

Natural killer cell-mimic nanoparticles can actively target and kill acute myeloid leukemia cells.

Natural killer (NK) cells play a crucial role in recognizing and killing emerging tumor cells. However, tumor cells develop mechanisms to inactivate NK cells or hide from them. Here, we engineered a modular nanoplatform that acts as NK cells (NK cell-mimics), carrying the tumor-recognition and death ligand-mediated tumor-killing properties of an NK cell, yet without being subject to tumor-mediated inactivation. NK cell mimic nanoparticles (NK.NPs) incorporate two key features of activated NK cells: cytotoxic activity via the death ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and an adjustable tumor cell recognition feature based on functionalization with the NK cell Fc-binding receptor (CD16, FCGR3A) peptide, enabling the NK.NPs to bind antibodies targeting tumor antigens. NK.NPs showed potent in vitro cytotoxicity against a broad panel of cancer cell lines. Upon functionalizing the NK.NPs with an anti-CD38 antibody (Daratumumab), NK.NPs effectively targeted and eliminated CD38-positive patient-derived acute myeloid leukemia (AML) blasts ex vivo and were able to target and kill CD38-positive AML cells in vivo, in a disseminated AML xenograft system and reduced AML burden in the bone marrow compared to non-targeted, TRAIL-functionalized liposomes. Taken together, NK.NPs are able to mimicking key antitumorigenic functions of NK cells and warrant their development into nano-immunotherapeutic tools