Chemically Programmed Vaccines: Iron Catalysis in Nanoparticles Enhances Combination Immunotherapy and Immunotherapy-Promoted Tumor Ferroptosis.

Immunotherapy has yielded impressive results, but only for a minority of patients with cancer. Therefore, new approaches that potentiate immunotherapy are a pressing medical need. Ferroptosis is a newly described type of programmed cell death driven by iron-dependent phospholipid peroxidation via Fenton chemistry.

Cancer Immunotherapy of TLR4 Agonist-Antigen Constructs Enhanced with Pathogen-Mimicking Magnetite Nanoparticles and Checkpoint Blockade of PD-L1.

Despite the tremendous potential of Toll-like receptor 4 (TLR4) agonists in vaccines, their efficacy as monotherapy to treat cancer has been limited. Only some lipopolysaccharides (LPS) isolated from particular bacterial strains or structures like monophosphoryl lipid A (MPLA) derived from lipooligosaccharide (LOS), avoid toxic overactivation of innate immune responses while retaining adequate immunogenicity to act as adjuvants. Here, different LOS structures are incorporated into nanoparticle-filled phospholipid micelles for efficient vaccine delivery and more potent cancer immunotherapy.

Effective cancer immunotherapy in mice by polyIC-imiquimod complexes and engineered magnetic nanoparticles.

Encouraging results are emerging from systems that exploit Toll like receptor (TLR) signaling, nanotechnology, checkpoint inhibition and molecular imaging for cancer immunotherapy. A major remaining challenge is developing effective, durable and tumour-specific immune responses without systemic toxicity. Here, we report a simple and versatile system based on synergistic activation of immune responses and direct cancer cell killing by combined TLR ligation using polyIC as TLR3 and imiquimod (R837) as TLR7 agonist, in combination with the model antigen ovalbumin (OVA) and phospholipid micelles loaded with zinc-doped iron oxide magnetic nanoparticles (MNPs).

Riboflavin as a bioorthogonal photocatalyst for the activation of a Pt prodrug.

Encouraging developments demonstrate that few transition metal and organometallic catalysts can operate in a bioorthogonal fashion and promote non-natural chemistry in living systems by minimizing undesired side reactions with cellular components. These catalytic processes have potential for applications in medicinal chemistry and chemical biology. However, the stringent conditions of the cell environment severely limit the number of accessible metal catalysts and exogenous reactions.

Correction: Near infrared activation of an anticancer Pt(IV) complex by Tm-doped upconversion nanoparticles.

Correction for 'Near infrared activation of an anticancer Pt(IV) complex by Tm-doped upconversion nanoparticles' by Emmanuel Ruggiero et al., Chem. Commun.

Upconverting Nanoparticles Prompt Remote Near-Infrared Photoactivation of Ru(II)-Arene Complexes.

The synthesis and full characterisation (including X-ray diffraction studies and DFT calculations) of two new piano-stool Ru(II) -arene complexes, namely [(η(6) -p-cym)Ru(bpy)(m-CCH-Py)][(PF)6]2 (1) and [(η(6) -p-cym)Ru(bpm)(m-CCH-Py)][(PF)6]2 (2; p-cym=p-cymene, bpy=2,2'-bipyridine, bpm=2,2'-bipyrimidine, and m-CCH-Py=3-ethynylpyridine), is described and discussed. The reaction of the m-CCH-Py ligand of 1 and 2 with diethyl-3-azidopropyl phosphonate by Cu-catalysed click chemistry affords [(η(6) -p-cym)Ru(bpy)(P-Trz-Py)][(PF)6]2 (3) and [(η(6) -p-cym)Ru(bpm)(P-Trz-Py)][(PF)6]2 (4; P-Trz-Py=[3-(1-pyridin-3-yl-[1,2,3]triazol-4-yl)-propyl]phosphonic acid diethyl ester). Upon light excitation at λ=395 nm, complexes 1-4 photodissociate the monodentate pyridyl ligand and form the aqua adduct ions [(η(6) -p-cym)Ru(bpy)(H2O)](2+) and [(η(6) -p-cym)Ru(bpm)(H2O)](2+).

Microdosed Lipid-Coated (67)Ga-Magnetite Enhances Antigen-Specific Immunity by Image Tracked Delivery of Antigen and CpG to Lymph Nodes.

Development of vaccines to prevent and treat emerging new pathogens and re-emerging infections and cancer remains a major challenge. An attractive approach is to build the vaccine upon a biocompatible NP that simultaneously acts as accurate delivery vehicle and radiotracer for PET/SPECT imaging for ultrasensitive and quantitative in vivo imaging of NP delivery to target tissues/organs. Success in developing these nanovaccines will depend in part on having a "correct" NP size and accommodating and suitably displaying antigen and/or adjuvants (e.

Photorelease of Pyridyl Esters in Organometallic Ru(II) Arene Complexes.

New Ru(II) arene complexes of formula [(η6-p-cym)Ru(N-N)(X)]2+ (where p-cym = para-cymene, N-N = 2,2'-bipyrimidine (bpm) or 2,2'-bipyridine (bpy) and X = m/p-COOMe-Py, 1-4) were synthesised and characterized, including the molecular structure of complexes [(η6-p-cym)Ru(bpy)(m-COOMe-Py)]2+ (3) and [(η6-p-cym)Ru(bpy) (p-COOMe-Py)]2+ (4) by single-crystal X-ray diffraction. Complexes 1-4 are stable in the dark in aqueous solution over 48 h and photolysis studies indicate that they can photodissociate the monodentate m/p-COOMe-Py ligands selectively with yields lower than 1%. DFT and TD-DFT calculations (B3LYP/LanL2DZ/6-31G**) performed on singlet and triplet states pinpoint a low-energy triplet state as the reactive state responsible for the selective dissociation of the monodentate pyridyl ligands.

An Iron Oxide Nanocarrier Loaded with a Pt(IV) Prodrug and Immunostimulatory dsRNA for Combining Complementary Cancer Killing Effects.

There is major current interest in harnessing the immune system against cancer and in developing drugs that provide complementary cancer killing mechanisms. Although the recent advent of nanoparticle-based drug delivery systems has improved the efficacy of platinum drugs for chemotherapy, one of the fundamental paradigms in their design and use is evading surveillance by the immune system to enhance anticancer efficacy. However, new studies are showing that chemotherapy can profit from actively targeting stimulation of the immune system and that suitably functionalized nanomaterials might be ideal for overcoming some key challenges in immunotherapy.

Near infrared activation of an anticancer Pt(IV) complex by Tm-doped upconversion nanoparticles.

The Pt(IV) complex cis,cis,trans-[Pt(NH3)2(Cl)2(O2CCH2CH2CO2H)2] is photoactivated by near infrared light (980 nm) using NaYF4:Yb(3+)/Tm(3+)@NaYF4 core-shell upconversion nanoparticles. Coupling of this cisplatin precursor with the biocompatible PEGylated phospholipid DSPE-PEG(2000)-NH2 affords a valuable approach to decorate the surface of the nanoparticles, providing novel photoactivatable nanomaterials capable of releasing Pt(II) species upon NIR light excitation.

An iron oxide nanocarrier for dsRNA to target lymph nodes and strongly activate cells of the immune system.

The success of nanoparticle-based therapies will depend in part on accurate delivery to target receptors and organs. There is, therefore, considerable potential in nanoparticles which achieve delivery of the right drug(s) using the right route of administration to the right location at the right time, monitoring the process by non-invasive molecular imaging. A challenge is harnessing immunotherapy via activation of Toll-like receptors (TLRs) for the development of vaccines against major infectious diseases and cancer.

Two novel ternary dicopper(II) μ-guanazole complexes with aromatic amines strongly activated by quantum dots for DNA cleavage.

Two novel (μ-guanazole)-bridged binuclear copper(II) complexes with 1,10-phenanthroline (phen) or 2,2'-bipyridine (bipy), [Cu2(μ-N2,N4-Hdatrz)(phen)2(H2O)(NO3)4] (1) and [Cu2(μ-N1,N2-datrz)2(μ-OH2)(bipy)2](ClO4)2 (2) (Hdatrz = 3,5-diamino-1,2,4-triazole = guanazole), have been prepared and characterized by X-ray diffraction, spectroscopy, and susceptibility measurements. Compounds 1 and 2 differ in the aromatic amine, which acts as a coligand, and in the Cu···Cu'-bridging system. Compound 1, which contains two mono-bridged copper ions, represents the first example of a discrete Cu-(NCN-trz)-Cu' complex.

QD-filled micelles which combine SPECT and optical imaging with light-induced activation of a platinum(IV) prodrug for anticancer applications.

The fac-[(99m)Tc(OH2)3(CO)3](+) complex reacts with QD-filled micelles to create a bimodal SPECT-optical imaging probe which upon visible light irradiation generates cisplatin from an inert Pt(IV) prodrug.

A dinucleating ligand which promotes DNA cleavage with one and without a transition metal ion.

The dinucleating ligand L (1,3-bis[bis(pyridin-2-ylmethyl)amino]propan-2-ol) combined with metal ions efficiently cleaves DNA when M : L is 1 : 1 (M = Co(II) or Fe(III)) at pH 5.5-7.0, with free L being more active at acidic pH than when bound to Zn(II), Cu(II) or Ni(II) at neutral pH.

Iron oxide-filled micelles as ligands for fac-[M(CO)3]+ (M = (99m)Tc, Re).

Magnetite-filled micelles capture fac-[M(OH(2))(3)(CO)(3)](+) complexes (M = (99m)Tc, Re), creating versatile self-assembled constructs for multimodal SPECT/MR/optical imaging and radiopharmaceutical guided delivery.

A turn-on fluorescence sensor for cyanide from mechanochemical reactions between quantum dots and copper complexes.

Manual grinding of CuCl(2), 2,2'-bipyridine and hydrophobic CdSe QDs creates a selective and fast turn-on fluorescence sensor for detection of nanogram quantities of solid cyanide salts by the naked-eye. Using a fluorescence detector this simple sensor detects 100 ppm of NaCN in sand.

Synergy between quantum dots and 1,10-phenanthroline-copper(II) complex towards cleaving DNA.

We have found that the DNA cleaving activity of quantum dots and 1,10-phenanthroline-Cu(II) complex is significantly enhanced when they are combined.

Quantum dots decorated with pathogen associated molecular patterns as fluorescent synthetic pathogen models.

We attached the pathogen associated molecular pattern Kdo(2)-Lipid A (the lipopolysaccharide (LPS) from Escherichia coli (E. coli)) to QDs by hydrophobic interactions to synthetically mimic the surface of E. coli.

Effective photoreduction of a Pt(IV) complex with quantum dots: a feasible new light-induced method of releasing anticancer Pt(II) drugs.

Irradiation of CdSe-ZnS quantum dots (QDs) with visible light in the presence of [PtCl(4)(bpy)] (1) (bpy = 2,2'-bipyridine) produced with high efficiency [PtCl(2)(bpy)] (2) by photoinduced electron transfer; a reaction and strategy which opens up new opportunities for cancer therapy.

Nitrilotriacetic acid-derivatized quantum dots for simple purification and site-selective fluorescent labeling of active proteins in a single step.

We demonstrate that QDs coated with nitrilotriacetic acid (NTA) bound to Ni (2+) can be used to reversibly and selectively bind, purify, and fluorescently label His 6-tagged (N-terminal) glutathione S-transferase (GST) in one step with retention of enzymatic activity. We find binding to be less effective in the absence of the His 6-tag or Ni (2+) ions.

Selective turn-on fluorescence detection of cyanide in water using hydrophobic CdSe quantum dots.

The ability of 2,2'-bipyridine-bound copper(ii) ions to quench the photoluminescence of hydrophobic CdSe quantum dots is used to create a novel, selective turn-on fluorescence cyanide sensor.

Cleavage and isomerization of UpU promoted by dinuclear metal ion complexes.

The catalysis of phosphoryl transfer by metal ions has been intensively studied in both biological and artificial systems, but the status of the transient pentacoordinate phosphoryl species (as transition state or intermediate) is the subject of considerable debate. We report that dinuclear metal ion complexes that incorporate second sphere hydrogen bond donors not only promote the cleavage of RNA fragments just as efficiently as the activated analogue HPNPP but also provide the first examples of metal ion catalyzed phosphate diester isomerization close to neutral pH. This observation implies that the reaction catalyzed by these complexes involves the formation of a phosphorane intermediate that is sufficiently long-lived to pseudorotate.

The combination of transition metal ions and hydrogen-bonding interactions.

This feature article presents an overview of the types of hydrogen bonding interactions involving metal complexes and their functional effects. It shows with recent examples why hydrogen bonds have become a crucial functional and structural element in modern inorganic chemistry. The relevance of this combination in tackling current chemistry challenges such as energy production and the development of new materials and more effective catalysts, sensors and medicines is illustrated.