Impact of Ligand Structure on Biological Activity and Photophysical Properties of NHC-Protected Au Nanoclusters.

N-heterocyclic carbene (NHC)-protected gold nanoclusters display high stability and high photoluminescence, making them well-suited for fluorescence imaging and photodynamic therapeutic applications. We report herein the synthesis of two bisNHC-protected Au nanoclusters with π-extended aromatic systems. Depending on the position of the π-extended aromatic system, changes to the structure of the ligand shell in the cluster are observed, with the ability to correlate increases in rigidity with increases in fluorescence quantum yield.

-Heterocyclic Carbene-Stabilized Atomically Precise Metal Nanoclusters.

This perspective highlights advances in the preparation and understanding of metal nanoclusters stabilized by organic ligands with a focus on -heterocyclic carbenes (NHCs). We demonstrate the need for a clear understanding of the relationship between NHC properties and their resulting metal nanocluster structure and properties. We emphasize the importance of balancing nanocluster stability with the introduction of reactive sites for catalytic applications and the importance of a better understanding of how these clusters interact with their environments for effective use in biological applications.

Combined thermal ablation and liposomal granulocyte-macrophage colony stimulation factor increases immune cell trafficking in a small animal tumor model.

Purpose: To characterize intratumoral immune cell trafficking in ablated and synchronous tumors following combined radiofrequency ablation (RFA) and systemic liposomal granulocyte-macrophage colony stimulation factor (lip-GM-CSF).

Methods: Phase I, 72 rats with single subcutaneous R3230 adenocarcinoma were randomized to 6 groups: a) sham; b&c) free or liposomal GM-CSF alone; d) RFA alone; or e&f) combined with blank liposomes or lip-GM-CSF. Animals were sacrificed 3 and 7 days post-RFA.

NHC-Stabilized Au Nanoclusters and Their Conversion to Au Nanoclusters.

Herein, we describe the synthesis of a toroidal Au cluster stabilized by -heterocyclic carbene and halide ligands reduction of the corresponding NHC-Au-X complexes (X = Cl, Br, I). The significant effect of the halide ligands on the formation, stability, and further conversions of these clusters is presented. While solutions of the chloride derivatives of Au show no change even upon heating, the bromide derivative readily undergoes conversion to form a biicosahedral Au cluster at room temperature.

N-Heterocyclic Carbene-Stabilized Hydrido Au Nanoclusters: Synthesis, Structure, and Electrocatalytic Reduction of CO.

Atomically precise hydrido gold nanoclusters are extremely rare but interesting due to their potential applications in catalysis. By optimization of molecular precursors, we have prepared an unprecedented N-heterocyclic carbene-stabilized hydrido gold nanocluster, [Au(NHC)ClH]. This cluster comprises a dimer of two Au kernels, each adopting an icosahedral shape with one missing vertex.

Synthesis and enantioseparation of chiral Au nanoclusters protected by bis--heterocyclic carbene ligands.

A series of chiral Au nanoclusters were synthesized the direct reduction of achiral dinuclear Au(i) halide complexes ligated by -xylyl-linked bis--heterocyclic carbene (NHC) ligands. A broad range of functional groups are tolerated as wingtip substituents, allowing for the synthesis of a variety of functionalized chiral Au nanoclusters. Single crystal X-ray crystallography confirmed the molecular formula to be [Au(bisNHC)Cl]Cl, with a chiral helical arrangement of the five bidentate NHC ligands around the icosahedral Au core.

Characterization of a Nanovaccine Platform Based on an α1,2-Mannobiose Derivative Shows Species-non-specific Targeting to Human, Bovine, Mouse, and Teleost Fish Dendritic Cells.

Dendritic cells serve as the main immune cells that trigger the immune response. We developed a simple and cost-effective nanovaccine platform based on the α1',2-mannobiose derivative for dendritic cell targeting. In previous work, we have formulated the α1,2-mannobiose-based nanovaccine platform with plasmid DNA and tested it in cattle against BoHV-1 infection.

Robust, Highly Luminescent Au Superatoms Protected by N-Heterocyclic Carbenes.

Gold superatom nanoclusters stabilized entirely by N-heterocyclic carbenes (NHCs) and halides are reported. The reduction of well-defined NHC-Au-Cl complexes produces clusters comprised of an icosahedral Au core surrounded by a symmetrical arrangement of nine NHCs and three chlorides. X-ray crystallography shows that the clusters are characterized by multiple CH-π and π-π interactions, which rigidify the ligand and likely contribute to the exceptionally high photoluminescent quantum yields observed, up to 16.

Radiofrequency ablation (RFA)-induced systemic tumor growth can be reduced by suppression of resultant heat shock proteins.

Purpose: To determine the role of hepatic radiofrequency ablation (RFA) heating parameters and their activation of heat shock proteins (HSPs) in modulating distant tumor growth.

Methods And Materials: First, to study the effects of RFA dose on distant tumor growth, rats with subcutaneous R3230 adenocarcinoma (10 ± 1 mm) were assigned to 3 different hepatic RF doses (60 °C × 10 min, 70 °C × 5 min or 90 °C × 2 min) that induced identical sized ablation or sham (n = 6/arm). Post-RFA tumor growth rates, cellular proliferation (Ki-67) and microvascular density (MVD) were compared at 7d.

Crystalline Superlattices of Nanoscopic CdS Molecular Clusters: An X-ray Crystallography and Cd SSNMR Spectroscopy Study.

Systematic Cd solid-state (SS) NMR experiments were performed to correlate X-ray crystallographic data with SSNMR parameters for a set of CdS-based materials, varying from molecular crystals of small complexes [Cd(SPh)] and [Cd(SPh)] to superlattices of large monodisperse clusters [CdS(SPh)(dmf)] and 1.9 nm CdS. Methodical data analysis allowed for assigning individual resonances or resonance groups to particular types of cadmium sites residing in different chemical and/or crystallographic environments.

Targeting STAT3 to Suppress Systemic Pro-Oncogenic Effects from Hepatic Radiofrequency Ablation.

Purpose To (a) identify key expressed genes in the periablational rim after radiofrequency ablation (RFA) and their role in driving the stimulation of distant tumor growth and (b) use adjuvant drug therapies to block key identified mediator(s) to suppress off-target tumorigenic effects of hepatic RFA. Materials and Methods This institutional animal care and use committee-approved study was performed in C57BL6 mice (n = 20) and F344 rats (n = 124). First, gene expression analysis was performed in mice after hepatic RFA or sham procedure; mice were sacrificed 24 hours to 7 days after treatment.

Luminescent CdSe Superstructures: A Nanocluster Superlattice and a Nanoporous Crystal.

Superstructures, combining nanoscopic constituents into micrometer-size assemblies, have a great potential for utilization of the size-dependent quantum-confinement properties in multifunctional electronic and optoelectronic devices. Two diverse superstructures of nanoscopic CdSe were prepared using solvothermal conversion of the same cadmium selenophenolate precursor (MeN)[Cd(SePh)]: the first is a superlattice of monodisperse [CdSe(SePh)(dmf)] nanoclusters; the second is a unique porous CdSe crystal. Nanoclusters were crystallized as cubic crystals (≤0.

Effect of thermal dose on heat shock protein expression after radio-frequency ablation with and without adjuvant nanoparticle chemotherapies.

Purpose: The aim of this study was to evaluate the effect of different radio-frequency ablation (RFA) thermal doses on coagulation and heat shock protein (HSP) response with and without adjuvant nanotherapies.

Materials And Methods: First, Fischer rats were assigned to nine different thermal doses of hepatic RFA (50-90 °C, 2-20 min, three per group) or no treatment (n = 3). Next, five of these RF thermal doses were combined with liposomal-doxorubicin (Lipo-Dox, 1 mg intravenously) in R3230 breast tumours, or no tumour treatment (five per group).

Stable -ESiMe3 Complexes of Cu(I) and Ag(I) (E=S, Se) with NHCs: Synthons in Ternary Nanocluster Assembly.

As a part of efforts to prepare new "metallachalcogenolate" precursors and develop their chemistry for the formation of ternary mixed-metal chalcogenide nanoclusters, two sets of thermally stable, N-heterocyclic carbene metal-chalcogenolate complexes of the general formula [(IPr)Ag-ESiMe3] (IPr=1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene; E=S, 1; Se, 2) and [(iPr2-bimy)Cu-ESiMe3]2 (iPr2-bimy=1,3-diisopropylbenzimidazolin-2-ylidene; E=S, 4; Se, 5) are reported. These are prepared from the reaction between the corresponding carbene metal acetate, [(IPr)AgOAc] and [(iPr-bimy)CuOAc] respectively, and E(SiMe3 )2 at low temperature. The reaction of [(IPr)Ag-ESiMe3] 1 with mercury(II) acetate affords the heterometallic complex [{(IPr)AgS}2Hg] 3 containing two (IPr)Ag-S(-) fragments bonded to a central Hg(II), representing a mixed mercury-silver sulfide complex.

Improved pharmacokinetics and enhanced tumor growth inhibition using a nanostructured lipid carrier loaded with doxorubicin and modified with a layer-by-layer polyelectrolyte coating.

A nanostructured lipid carrier (NLC) loaded with doxorubicin (DOX) has been shown to be cytotoxic against the human cancer cell lines A549 and MCF-7/Adr. In attempts to improve formulation characteristics, enhance pharmacokinetics and antitumor effects, we modified the surface of these NLC with an alternating layer-by-layer (LbL) assembly of polycation and polyanion polyelectrolytes and an additional coating with PEG using a simple method of core shell attachment. The formulation had a narrow size distribution, longer residence in the blood, lower accumulation in the liver, higher accumulation in tumors and a significant tumor growth inhibition effect.

Systemic siRNA Nanoparticle-Based Drugs Combined with Radiofrequency Ablation for Cancer Therapy.

Purpose: Radiofrequency thermal ablation (RFA) of hepatic and renal tumors can be accompanied by non-desired tumorigenesis in residual, untreated tumor. Here, we studied the use of micelle-encapsulated siRNA to suppress IL-6-mediated local and systemic secondary effects of RFA.

Methods: We compared standardized hepatic or renal RFA (laparotomy, 1 cm active tip at 70 ± 2 °C for 5 min) and sham procedures without and with administration of 150 nm micelle-like nanoparticle (MNP) anti-IL6 siRNA (DOPE-PEI conjugates, single IP dose 15 min post-RFA, C57Bl mouse:3.

Polydentate chalcogen reagents for the facile preparation of Pd2 and Pd4 complexes.

The silylated organochalcogen reagents 1,2-(Me3SiSCH2)2C6H4, and 1,2-(Me3SiSeCH2)2C6H4, were prepared from the corresponding organobromides and lithium trimethylsilanechalcogenolate Li[ESiMe3] (E = S, Se). They have been characterized by multinuclear NMR spectroscopy ((1)H, (13)C, (77)Se) and electrospray ionization mass spectrometry. and react under mild conditions with (1,3-bis(diphenylphosphino)propane)palladium(ii) chloride, [PdCl2(dppp)], to provide the dinuclear organochalcogenolate-bridged complexes [(dppp)2Pd2-μ-κ(2)S-{1,2-(SCH2)2C6H4}]X2, []X2 and [(dppp)2Pd2-μ-κ(2)Se-{1,2-(SeCH2)2C6H4}]X2, []X2 (X = Cl, Br) in good yield, respectively.

Radiofrequency ablation-induced upregulation of hypoxia-inducible factor-1α can be suppressed with adjuvant bortezomib or liposomal chemotherapy.

Purpose: To characterize upregulation of hypoxia-inducible factor (HIF)-1α after radiofrequency (RF) ablation and the influence of an adjuvant HIF-1α inhibitor (bortezomib) and nanodrugs on modulating RF ablation-upregulated hypoxic pathways.

Materials And Methods: Fisher 344 rats (n = 68) were used. First, RF ablation-induced periablational HIF-1α expression was evaluated in normal liver or subcutaneous R3230 tumors (14-16 mm).

Nanodrug-enhanced radiofrequency tumor ablation: effect of micellar or liposomal carrier on drug delivery and treatment efficacy.

Purpose: To determine the effect of different drug-loaded nanocarriers (micelles and liposomes) on delivery and treatment efficacy for radiofrequency ablation (RFA) combined with nanodrugs.

Materials/methods: Fischer 344 rats were used (n = 196). First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of i.

In vitro transfection of bone marrow-derived dendritic cells with TATp-liposomes.

Dendritic cells (DC) are antigen-presenting cells uniquely capable of priming naïve T cells and cross-presenting antigens, and they determine the type of immune response elicited against an antigen. TAT peptide (TATp), is an amphipathic, arginine-rich, cationic peptide that promotes penetration and translocation of various molecules and nanoparticles into cells. TATp-liposomes (TATp-L) used for DC transfection were prepared using TATp derivatized with a lipid-terminated polymer capable of anchoring in the liposomal membrane.

Layer-by-layer nanoencapsulation of camptothecin with improved activity.

160 nm nanocapsules containing up to 60% of camptothecin in the core and 7-8 polyelectrolyte bilayers in the shell were produced by washless layer-by-layer assembly of heparin and block-copolymer of poly-l-lysine and polyethylene glycol. The outer surface of the nanocapsules was additionally modified with polyethylene glycol of 5 kDa or 20 kDa molecular weight to attain protein resistant properties, colloidal stability in serum and prolonged release of the drug from the capsules. An advantage of the LbL coated capsules is the preservation of camptothecin lactone form with the shell assembly starting at acidic pH and improved chemical stability of encapsulated drug at neutral and basic pH, especially in the presence of albumin that makes such formulation more active than free camptothecin.

Adjuvant liposomal doxorubicin markedly affects radiofrequency ablation-induced effects on periablational microvasculature.

Purpose: To evaluate the effects of radiofrequency (RF) ablation without and with adjuvant intravenous (IV) liposomal doxorubicin (Doxil) on microvessel morphology and patency and intratumoral drug delivery and retention.

Materials And Methods: There were 133 tumors/animals used in this experiment. First, single subcutaneous tumors (R3230 in Fischer rats and 786-0 in nude mice) were randomly assigned to receive RF ablation alone or no treatment and sacrificed 0-72 hours after treatment.

Long-circulating PEG-PE micelles co-loaded with paclitaxel and elacridar (GG918) overcome multidrug resistance.

Overexpression of drug efflux pump P-gp is one of the major reasons to cause multidrug resistance (MDR). To overcome P-gp mediated MDR, modulators, so called P-gp inhibitors, can be used to block efflux pump activity. Elacridar is one of the most potent P-gp inhibitors, which can cause irreversible and total P-gp blockage.

Liposomes for cardiovascular targeting.

Liposome-based pharmaceuticals used within the cardiovascular system are reviewed in this article. The delivery of diagnostic and therapeutic agents by plain liposomes and liposomes with surface-attached targeting antibodies or polyethylene glycol to prolong their circulation time and accumulation at vascular injuries, ischemic zones or sites of thrombi are also discussed. An overview of the advantages and disadvantages of liposome-mediated in vitro, ex vivo and in vivo targeting is presented, including discussion of the targeting of liposomes to pathological sites on the blood vessel wall and a description of liposomes that can be internalized by endothelial cells.