Albumin is the most abundant protein in human serum and drugs that are administered intravenously inevitably interact with it. We present here a series of platinum(IV) prodrugs designed specifically to enhance interaction albumin (HSA) for drug delivery. This goal achieved by asymmetrically functionalizing axial ligands prodrug so as mimic overall features fatty acid. Systematic variation length aliphatic tail tunes cellular uptake and, consequently, cytotoxicity...

Abstract Therapeutic nanoparticles (TNPs) aim to deliver drugs more safely and effectively cancers, yet clinical results have been unpredictable owing limited in vivo understanding. Here we use single-cell imaging of intratumoral TNP pharmacokinetics pharmacodynamics better comprehend their heterogeneous behaviour. Model TNPs comprising a fluorescent platinum(IV) pro-drug clinically tested polymer platform (PLGA- b -PEG) promote long drug circulation alter accumulation by directing cellular...

A novel approach toward the construction of multicomponent two-dimensional (2-D) and three-dimensional (3-D) metallosupramolecules is reported. Simply by mixing carboxylate pyridyl ligands with cis-Pt(PEt3)2(OTf)2 in a proper ratio, coordination-driven self-assembly occurs, allowing for selective generation discrete structures via charge separation on metal centers. Using this method, variety 2-D rectangles 3-D prisms were prepared under mild conditions. Moreover, can also be achieved...

This report presents a novel strategy that facilitates delivery of multiple, specific payloads Pt(IV) prodrugs using well-defined supramolecular system. system comprises hexanuclear Pt(II) cage can host four prodrug guest molecules. Relying on host-guest interactions between adamantyl units tethered to the molecules and cage, could be encapsulated within one cage. complex, exhibiting diameter about 3 nm, has been characterized by detailed NMR spectroscopic measurements. Owing high positive...

The design and preparation of novel M(3)L(2) trigonal cages via the coordination-driven self-assembly preorganized metalloligands containing octahedral aluminum(III), gallium(III), or ruthenium(II) centers is described. When tritopic dinuclear linear appropriate complementary subunits are employed, trigonal-bipyramidal trigonal-prismatic self-assembled under mild conditions. These three-dimensional were characterized with multinuclear NMR spectroscopy ((1)H (31)P) high-resolution...

Phenanthriplatin, cis-[Pt(NH3)2Cl(phenanthridine)](NO3), is a cationic monofunctional DNA-binding platinum(II) anticancer drug candidate with unusual potency and cellular response profiles. Its in vivo efficacy has not yet been demonstrated, highlighting the need for delivery system. Here we report tobacco mosaic virus (TMV) as system phenanthriplatin. TMV forms hollow nanotubes polyanionic interior surface; capitalizing on this native structure, developed one-step phenanthriplatin loading...

We present a general strategy for the synthesis of stable 3-D metallosupramolecular tetragonal prisms in which multicomponent coordination-driven self-assembly allows single supramolecular species to be formed. The appropriate stoichiometric combination tetraphenylethylene-based tetratopic donor (1), linear dipyridine (2), and 90° platinum metal complex (3) affords (4) as products. compounds have been characterized by multinuclear NMR spectroscopy electrospray ionization mass spectrometry....

Expression of indoleamine-2,3-dioxygenase (IDO), an immunosuppressive enzyme in human tumors, leads to immune evasion and tumor tolerance. IDO is therefore a immunotherapeutic target, several inhibitors are currently undergoing clinical trials. can enhance the efficacy common cancer chemotherapeutics. Here we investigate Pt(IV)-(D)-1-methyltryptophan conjugates 1 2 for combined immunomodulation DNA cross-link-triggered apoptosis "immuno-chemotherapy". Compound effectively kills...

Post-self-assembly modifications of a discrete metal–organic supramolecular structure have been developed. Such allow the properties self-assembled species to be changed in simple and efficient manner (>90% yield). Initiated by application chemical stimuli, post-self-assembly described herein result three distinct changes system: an individual building-block component change, overall structural modification, functional evolution [6+4] structure. The carefully examined range characterization...

A method of incorporating both metal−ligand and crown ether−dialkylammonium self-assembly techniques in the efficient synthesis metallacyclic tris[2]pseudorotaxanes is described. These multifunctional supramolecules can be prepared by stepwise or one-pot assembly nine separate components on account orthogonality two noncovalent strategies employed. This methodology demonstrates power orthogonal may expanded beyond use recognition motifs hopes mimicking complex multifunctionality biological systems.

The synthesis of a new 120 degree diplatinum(II) acceptor unit and the self-assembly series two-dimensional metallacyclic polypseudorotaxanes that utilize both metal-ligand crown ether-dialkylammonium noncovalent interactions are described. Judiciously combining complementary acceptors with bispyridyl donor building blocks, an and/or possessing pendant dibenzo[24]crown-8 (DB24C8) moiety, allows for formation three rhomboidal bis-DB24C8, one hexagonal tris-DB24C8, four hexakis-DB24C8 polygons...

The multicomponent coordination-driven self-assembly of hexakis[4-(4-pyridyl)phenyl]benzene, cis-(PEt3)2PtII(OTf)2, and amine- or maleimide-functionalized isophthalate forms discrete hexagonal prisms as single reaction products. amino maleimide groups decorating the pillars provide reactive sites for post-self-asssembly modifications. In this communication, we demonstrate that can be functionalized without disrupting prismatic cores, enabling incorporation new functionalities under mild conditions.

The effect of a newly developed osmium(VI) nitrido complex, 1, on breast cancer stem cells (CSCs) is reported. complex displays selective toxicity for HMLER enriched with CD44-positive, CSC-like over the same having reduced CSC character. Remarkably, 1 also reduces proportion CSCs within heterogeneous cell population and irreversibly inhibits formation free-floating mammospheres to an extent similar that salinomycin, natural product targets CSCs. Detailed mechanistic studies reveal in...

Rhenium(V) oxo complexes of general formula [ReO(OMe)(N^N)Cl2], where N^N = 4,7-diphenyl-1,10-phenanthroline, 1, or 3,4,7,8-tetramethyl-1,10-phenanthroline, 2, effectively kill cancer cells by triggering necroptosis, a non-apoptotic form cell death. Both evoke necrosome (RIP1-RIP3)-dependent intracellular reactive oxygen species (ROS) production and propidium iodide uptake. The also induce mitochondrial membrane potential depletion, possible downstream effect ROS production. Apparently, 1 2...

RNAi approaches have been widely combined with platinum-based anticancer agents to elucidate cellular responses and target gene products that mediate acquired resistance. Recent work has demonstrated platination of siRNA prior transfection may negatively influence efficiency based on the position sequence its guanosine nucleosides. Here, we used detailed spectroscopic characterization demonstrate rapid formation Pt-guanosine adducts within 30 min after coincubation oxaliplatin [OxaPt(II)] or...

Abstract The self‐organization of multicomponent supramolecular systems involving a variety two‐dimensional (2 D) polygons and three‐dimensional (3 cages is presented. Nine self‐organizing systems, SS 1 – 9 , have been studied. Each involves the simultaneous mixing organoplatinum acceptors pyridyl donors varying geometry their selective self‐assembly into three to four specific 2 D (rectangular, triangular, rhomboid) and/or 3 (triangular prism distorted nondistorted trigonal bipyramidal)...

Size selective self-sorting in the coordination-driven self-assembly of two-dimensional (2-D) polygons and three-dimensional (3-D) cages is presented. Two types (rectangular triangular) different size are formed spontaneously from within mixtures a molecular "clip" or 60° organoplatinum acceptor with dipyridyl linkers lengths via self-sorting. Furthermore, two sized 3-D supramolecular upon mixing one ditopic tritopic donors process. The formation these characterized using NMR spectroscopy...

The direct observation of dynamic ligand exchange between Pt-N coordination-driven self-assembled supramolecular polygons (triangles and rectangles) has been achieved using stable (1)H/(2)D isotope labeling the pyridyl donors electrospray ionization mass spectrometry combined with NMR spectroscopy. Both thermodynamic kinetic aspects such processes have established on basis quantitative spectral results. Further investigation shown that is highly dependent experimental conditions as...

A new approach wherein steric interactions between substituents of unsymmetrical bis(4-pyridyl)acetylene ligands dictate the self-selection single isomers [4 + 4] self-assembled squares is presented. Each self-assembly characterized by multinuclear 31P and 1H NMR spectroscopies electrospray ionization mass spectrometry. spectroscopic studies are used to provide a means evaluating efficiency bulky at proximal or remote positions relative Pt−N bonding motif direct self-selection. Molecular...

This article presents a new strategy to engage coordination-driven self-assembly for platinum drug delivery. The self-assembled supramolecular hexagon is conjugated with three equivalents of Pt(iv) prodrugs and displays superior therapeutic index compared cisplatin against panel human cancer cell lines.

The fatty acid-like Pt(<sc>iv</sc>) prodrugs act as a “Trojan horse” to exploit upregulated CD36 receptors facilitate their entry ovarian cancer cells.

The construction of a new series dendritic tris(crown ether) hexagons via coordination-driven self-assembly is described. Combining 120° crown ether-containing diplatinum(II) acceptors with dipyridyl donors in 1:1 ratio allows for the formation family triple ether derivatives hexagonal cavity quantitative yields. number and position these pendant groups can be precisely controlled on metallacycle. structures all multiple hexgaons are confirmed by multinuclear NMR ((1)H (31)P), ESI-MS...