Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

BACKGROUND: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. RESULTS: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. CONCLUSIONS: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

Synergistic photothermal-photodynamic-chemotherapy toward breast cancer based on a liposome-coated core-shell AuNS@NMOFs nanocomposite encapsulated with gambogic acid.

A multifunctional nanoplatform with core-shell structure was constructed in one-pot for the synergistic photothermal, photodynamic, and chemotherapy against breast cancer. In the presence of gambogic acid (GA) as the heat-shock protein 90 (HSP90) inhibitor and the gold nanostars (AuNS) as the photothermal reagent, the assembly of Zr4+ with tetrakis (4-carboxyphenyl) porphyrin (TCPP) gave rise to the nanocomposite AuNS@ZrTCPP-GA (AZG), which in turn, further coated with PEGylated liposome (LP) to enhance the stability and biocompatibility, and consequently the antitumor effect of the particle. Upon cellular uptake, the nanoscale metal - organic framework (NMOF) of ZrTCPP in the resulted AuNS@ZrTCPP-GA@LP (AZGL) could be slowly degraded in the weak acidic tumor microenvironment to release AuNS, Zr4+, TCPP, and GA to exert the synergistic treatment of tumors via the combination of AuNS-mediated mild photothermal therapy (PTT) and TCPP-mediated photodynamic therapy (PDT). The introduction of GA serves to reduce the thermal resistance of the cell to re-sensitize PTT and the constructed nanoplatform demonstrated remarkable anti-tumor activity in vitro and in vivo. Our work highlights a facile strategy to prepare a pH-dissociable nanoplatform for the effective synergistic treatment of breast cancer.

One Unique 1D Silver(I)-Bromide-Thiol Coordination Polymer Used for Highly Efficient Chemiresistive Sensing of Ammonia and Amines in Water.

Reaction of AgBr with TabHPF6 (TabH = 4-(trimethylammonio)benzenethiol) readily produces a unique one-dimensional coordination polymer [(TabH)(AgBr2)]n (1), consisting of anionic chains [AgBr2]n(n-) with hydrogen bonds to TabH(+) cations. By examining its electrical resistance and stability upon exposure to ammonia and seven common organic amines in water under ambient conditions, compound 1 is found to exhibit good stability and reproducibly high sensitivity toward these analytes at low concentrations. Especially, it can selectively detect NH3 in water with the detection limit as low as 0.05 ppm. This chemiresistive sensing system has the potential for highly efficient monitoring of ammonia and amines responsible for water pollution, eutrophication, food contamination, and industrial hazards.

Synthesis and transmembrane anion/cation symport activity of a rigid bis(choloyl) conjugate functionalized with guanidino groups.

A rigid bis(choloyl) conjugate functionalized with guanidino groups was synthesized and fully characterized on the basis of NMR ((1)H and (13)C) and ESI MS (LR and HR) data. Its transmembrane ionophoric activity across egg-yolk l-α-phosphatidylcholine-based liposomal membranes was investigated by means of chloride ion selective electrode technique and pH discharge assay. The data indicate that under the assay conditions, this conjugate was capable of promoting the transport of anions, presumably via a cation/anion symport process. A Hill analysis reveals that two molecules of this compound are assembled into the transport-active species.

Synthesis and potent ionophoric activity of a squaramide-linked bis(choloyl) conjugate.

A squaramide-linked bis(choloyl) conjugate was synthesized and fully characterized on the basis of NMR ((1)H and (13)C) and ESI MS (LR and HR) data. Fluorescence and chloride ion selective electrode assays indicate that this compound exhibits potent ionophoric activity across egg-yolk L-α-phosphatidylcholine-based liposomal membranes, presumably via an anion-modulating anion-cation co-transport/symport process. A Hill analysis reveals that three molecules of this compound are assembled into the transport-active species.

Transmetalation of a dodecahedral Na9 aggregate-based polymer: a facile route to water stable Cu(II) coordination networks.

A variety of network structures have been prepared by transmetalation of a polymer {Na3[Na9(Cbdcp)6(H2O)18]}n (1) (Cbdcp = N-(4-carboxybenzyl)-(3,5-dicarboxyl)pyridinium) containing dodecahedral Na9 aggregate secondary building units with Cu(II) by modulating the temperature, solvent, and pH. These complexes include a large, zwitterionic hexa-cuprometallocycle [Cu6(Cbdcp)6(H2O)18] (2) formed in H2O at room temperature, two three-dimensional polymers [Cu3(Cbdcp)2(OH)2(H2O)2]n (3) and {[Cu3(Cbdcp)2(OH)2]·2H2O}n (4) isolated from H2O and DMF/H2O at 135 °C, and a mononuclear complex [Cu(HCbdcp)2(H2O)3]·H2O (5) from H2O at 100 °C and pH = 6. All the complexes are robust and water stable. The crystal framework of macrocycle 2 is stable up to 100 °C under vacuum and selectively adsorbs CO2.

Stitching 2D polymeric layers into flexible interpenetrated metal-organic frameworks within single crystals.

A 2D coordination polymer prepared with bulky diethylformamide solvates exhibits channels which allow dipyridyl bridging ligands to diffuse into the crystal lattice. The absorbed dipyridyls thread through the pores of one layer and substitute the surface diethylformamide molecules on the neighboring layers to stitch alternate layers to form flexible interpenetrated metal-orgaic frameworks. The threading process also results in exchange of the bulky diethylformamide solvates for aqua to minimize congestion and, more strikingly, forces the slippage of two-dimensional layers, while still maintaining crystallinity.

Synthesis and anionophoric activities of dimeric polyamine-sterol conjugates: the impact of rigid vs. flexible linkers.

Two dimeric spermine-choloyl conjugates were synthesized and found to be capable of promoting the transport of anions across egg-yolk L-α-phosphatidylcholine-based liposomal membranes, via an anion-exchange mechanism and with moderate selectivity with respect to monoanionic ions. A Hill analysis indicated that these two conjugates exhibited similar aggregation behaviors. However, the conjugate bearing a rigid p-bis(aminomethyl)benzene moiety functioned more efficiently than the analogue having a flexible putrescine linker.

Facile synthesis of a dimeric dipyrrole-polyamide and synergetic DNA-cleaving activity of its Cu(II) complex.

Inspired by the potent DNA-cleaving activity of the Cu(II) complex of monopyrrole-polyamide dimer 1 (i.e., 1@Cu(2+)), we designed a new dimeric dipyrrole-polyamide analog 2 with the aim to optimize the catalytic activities of the metal complexes of this type of polypyrrole-polyamides. Compound 2 was prepared in 50% yield from the reaction of 1-methyl-4-[(1-methyl-4-nitro-1H-pyrrole-2-carbonyl)-amino]-1H-pyrrole-2-carboxylic acid with 2,2'-(ethane-1,2-diylbis(oxy))diethanamine, and fully characterized on the basis of NMR ((1)H and (13)C), MS (ESI and HR) and IR. Spectrophotometric titration, ESI-MS and conductivity measurements indicated that compound 2 formed a 1:1 complex with Cu(2+) ion (i.e., 2@Cu(2+)). Agarose gel electrophoresis studies indicated that 2@Cu(2+) was capable of efficiently converting pBR322 DNA into open circular and linear forms under physiological conditions, most probably via an oxidative mechanism. Its overall catalytic activity was estimated to be at least 30-fold higher than that of 1@Cu(2+). The fact that the cleaving activities of these Cu(II) complexes parallel, exactly, their binding affinities, raises the possibility that the cleaving activities of polypyrrole-polyamide derivatives of the type can be regulated by the binding affinities.

Synergetic DNA-cleaving activities of the metal complexes of a polyether-tethered pyrrole-polyamide dimer.

A simple polyether-tethered pyrrole-polyamide dimer 1 was synthesized in 50% yield from the reaction of 2,2,2-trichloro-1-(1-methyl-4-nitro-1H-pyrrol-2-yl)ethanone with 2,2'-[1,2-ethanediylbis(oxy)]bisethanamine, and fully characterized on the basis of ¹H- and ¹³C-NMR, MS, HR-MS, and IR data. Agarose gel-electrophoresis study of the cleavage of plasmid pBR322 DNA by the complexes of compound 1 with seven metal ions indicated that most of the metal complexes were capable of efficiently cleaving DNA at pH 7.0 and 37°. Among them, the Cu(II) complex exhibited the highest activity, with the maximal catalytic rate constant k(max) and Michaelis constant K(M) being 5.61 h⁻¹ and 7.30 mM, respectively. Spectroscopic, ESI-MS, ethidium-bromide (EB) displacement, and viscosity experiments indicated that compound 1 could form a 1 : 1 complex with Cu(II) ion, and that this complex showed moderate binding affinity toward calf-thymus DNA.

NIR-PTT/ROS-Scavenging/Oxygen-Enriched Synergetic Therapy for Rheumatoid Arthritis by a pH-Responsive Hybrid CeO2-ZIF-8 Coated with Polydopamine.

Rheumatoid arthritis (RA) is an inflammatory type of arthritis that causes joint pain and damage. The inflammatory cell infiltration (e.g., M1 macrophages), the poor O2 supply at the joint, and the excess reactive oxygen species (ROS)-induced oxidative injury are the main causes of RA. We herein report a polydopamine (PDA)-coated CeO2-dopped zeolitic imidazolate framework-8 (ZIF-8) nanocomposite CeO2-ZIF-8@PDA (denoted as CZP) that can synergistically treat RA. Under near-infrared (NIR) light irradiation, PDA efficiently scavenges ROS and results in an increased temperature in the inflamed area because of its good light-to-heat conversion efficiency. The rise of temperature serves to obliterate hyper-proliferative inflammatory cells accumulated in the diseased area while vastly promoting the collapse of the acidic-responsive skeleton of ZIF-8 to release the encapsulated CeO2. The released CeO2 exerts its catalase-like activity to relieve hypoxia by generating oxygen via the decomposition of H2O2 highly expressed in the inflammatory sites. Thus, the constructed CZP composite can treat RA through NIR-photothermal/ROS-scavenging/oxygen-enriched combinative therapy and show good regression of pro-inflammatory cytokines and hypoxia-inducible factor-1α (HIF-1α) in vitro and promising therapeutic effect on RA in rat models. The multimodal nano-platform reported herein is expected to shed light on the design of synergistic therapeutic nanomedicine for effective RA therapy.

A zwitterionic 1D/2D polymer co-crystal and its polymorphic sub-components: a highly selective sensing platform for HIV ds-DNA sequences.

Polymorphic compounds {[Cu(dcbb)2(H2O)2]·10H2O}n (2, 1D chain), [Cu(dcbb)2]n (3, 2D layer) and their co-crystal {[Cu(dcbb)2(H2O)][Cu(dcbb)2]2}n (4) have been prepared from the coordination reaction of a 2D polymer [Na(dcbb)(H2O)]n (1, H2dcbbBr = 1-(3,5-dicarboxybenzyl)-4,4'-bipyridinium bromide) with Cu(NO3)2·3H2O at different temperatures in water. Compounds 2-4 have an identical metal-to-ligand stoichiometric ratio of 1 : 2, but absolutely differ in structure. Compound 3 features a 2D layer structure with aromatic rings, positively charged pyridinium and free carboxylates on its surface, promoting electrostatic, π-stacking and/or hydrogen-bonding interactions with the carboxyfluorescein (FAM) labeled probe single-stranded DNA (probe ss-DNA, delineates as P-DNA). The resultant P-DNA@3 system facilitated fluorescence quenching of FAM via a photoinduced electron transfer process. The P-DNA@3 system functions as an efficient fluorescent sensor selective for HIV double-stranded DNA (HIV ds-DNA) due to the formation of a rigid triplex structure with the recovery of FAM fluorescence. The system reported herein also distinguishes complementary HIV ds-DNA from mismatched target DNA sequences with the detection limit of 1.42 nM.

Five water-soluble zwitterionic copper(II)-carboxylate polymers: role of dipyridyl coligands in enhancing the DNA-binding, cleaving and anticancer activities.

Five water-soluble zwitterionic copper-carboxylate polymers were prepared from the reaction of N-carboxymethyl-(3,5-dicarboxyl)pyridinium bromide (H3CmdcpBr) with Cu(NO3)2 in the presence of NaOH by modulating the temperature, solvent and ancillary dipyridyl ligands. These complexes include a 1D ladder-shaped polymer {[Cu3(Cmdcp)2(OH)2(H2O)2]·H2O}n () formed in H2O at room temperature, and a 2D network polymer {[Cu(Cmdcp) (H2O)2]·2H2O}n () isolated in H2O at 135 °C. At 100 °C in H2O/DMF, the same reaction in the presence of an additional 2,2'-bipyridine (bipy) gave a 2D zwitterionic complex {[Cu(Cmdcp)(bipy)]·3H2O}n () together with a 1D double-stranded polymer {[Cu(Cmdcp)(H2O)2]·H2O}n () as a minor product. The replacement of bipy with phenanthroline (phen) afforded a 1D zigzag polymer chain {[Cu(Cmdcp)(phen)(H2O)]2·9H2O}5 (). All these complexes were characterized by IR, elemental analyses and single crystal X-ray crystallography. Agarose gel electrophoresis (GE) and ethidium bromide (EB) displacement experiments indicated that complex exhibited the highest pBR322 DNA cleaving ability with the catalytic efficiency (kmax/KM) of 14.80 h(-1) mM(-1) and the highest binding affinity toward calf-thymus DNA. The MTT assay indicated that complex showed significant inhibitory activity toward the proliferation of several tumor cells. Its IC50 value was at micromolar level and lower than those of cisplatin and complexes , especially toward resistant lung adenocarcinoma cell A549.

Synthesis, hydrolytic DNA-cleaving activities and cytotoxicities of EDTA analogue-tethered pyrrole-polyamide dimer-based Ce(IV) complexes.

Two EDTA analogue-tethered C2-symmetrical dimeric monopyrrole-polyamide 5 and dipyrrole-polyamide 6, and their corresponding Ce(IV) complexes Ce-5 and Ce-6 were synthesized and fully characterized. Agarose gel electrophoresis studies on pBR322 DNA cleavage indicate that complexes Ce-5 and Ce-6 exhibited potent DNA-cleaving activities under physiological conditions. The maximal first-order rate constants (kmax's) were (0.42 ± 0.02) h(-1) for Ce-5 and (0.52 ± 0.02) h(-1) for Ce-6, respectively, suggesting that both complexes catalyzed the cleavage of supercoiled DNA by up to approximately 10(8)-fold. Complex Ce-6 exhibited ca 10-fold higher overall catalytic activity (kmax/KM) than Ce-5, which may be ascribed to its higher DNA-binding affinity. Inhibition experiments and a model study convincingly suggest that both complexes Ce-5 and Ce-6 functioned as hydrolytic DNA-cleavers. In addition, both complexes were found to display moderate inhibitory activity toward A549 and HepG-2 cells.

Synthesis, DNA-cleaving activities and cytotoxicities of C2-symmetrical dipyrrole-polyamide dimer-based Cu(II) complexes: a comparative study.

Two C2-symmetrical dipyrrole-polyamide dimers 2 and 3 that were tethered with triethylenetetramine and spermine, respectively, and their corresponding Cu(II) complexes 2@Cu(2+) and 3@Cu(2+), were synthesized and fully characterized. Agarose gel electrophoresis studies on pBR322 DNA cleavage indicated that both Cu(II) complexes exhibited potent DNA-cleaving activities under physiological conditions, most probably via an oxidative mechanism. Kinetic assay indicate that 2@Cu(2+) and 3@Cu(2+) exhibited comparable catalytic efficiency with the Cu(II) complex of their 2,2'-(ethane-1,2-diylbis(oxy))diethanamine-tethered analog 1. The finding that compounds 2 and 3 showed higher Cu(II) ion-complexing abilities than compound 1, suggests that strong metal complexation does not necessarily lead to an enhancement in the catalytic efficiency of a DNA-cleaving agent. In addition, three Cu(II) complexes displayed moderate inhibitory activities toward three tumor cell lines.