Adaptive Responses of a Peroxidase-like Polyoxometalate-Based Tri-Assembly to Bacterial Microenvironment (BME) Significantly Improved the Anti-Bacterial Effects.

The present study presents the tertiary assembly of a POM, peptide, and biogenic amine, which is a concept to construct new hybrid bio-inorganic materials for antibacterial applications and will help to promote the development of antivirus agents in the future. To achieve this, a Eu-containing polyoxometalate (EuW10) was first co-assembled with a biogenic amine of spermine (Spm), which improved both the luminescence and antibacterial effect of EuW10. Further introduction of a basic peptide from HPV E6, GL-22, induced more extensive enhancements, both of them being attributed to the cooperation and synergistic effects between the constituents, particularly the adaptive responses of assembly to the bacterial microenvironment (BME). Further intrinsic mechanism investigations revealed in detail that the encapsulation of EuW10 in Spm and further GL-22 enhanced the uptake abilities of EuW10 in bacteria, which further improved the ROS generation in BME via the abundant H2O2 involved there and significantly promoted the antibacterial effects.

Hyaluronic Acid-Enwrapped Polyoxometalate Complex for Synergistic Near Infrared-II Photothermal/Chemo-Therapy and Chemodynamic Therapy.

To enhance the efficacy of tumor therapy, the collection of functional components into a targeting system shows advantages over most homogeneous materials in inducing apoptosis of cancer cells. The security and targeting of therapeutic agents also require the effect combination of additional components. However, the construction of multifunctional composites in a simple system with intelligent cooperative responsiveness remains a challenge. Herein, a reduced polyanionic cluster (rP2W18) bearing the absorption at the near infrared (NIR) II region is used as a core carrier to bind the positively charged doxorubicin hydrochloride (DOX) through ionic interaction. To reduce the physiological toxicity, hyaluronic acid grafting ß-cyclodextrin side chains is used to cover the ionic complex through host-guest inclusion to DOX. When the nanocomposite is activated by local laser exposure, the final three-component therapeutic agent is demonstrated to present targeted photothermal conversion capability and chemodynamic activity together with chemotherapy. With the controlled release of DOX under the stimulation of mild acidity in the tumor region and photothermal effect, the exposed rP2W18 is aroused by hydrogen peroxide overexpressed in a tumor microenvironment to produce toxic reactive oxygen species, 1O2. This work presents an opportunity for the development of a nanocomposite in NIR-II photothermal/chemo-therapy and chemodynamic synergistic therapy.

Biocompatible Polymer Nanocomposites Integrating Magnetic Polyoxomolybdates for Enhanced MRI and On-Site Activated Photothermal Properties.

This work reports the ionic composition of a PEGylated and chemically crosslinked polyethyleneimine with a gadolinium-coordinated polyoxomolybdate cluster, K17 [Gd(P2 Mo17 O61 )2 ], via electrostatic interaction. The prepared composites form nanoobjects with an average size of ≈27 nm at dried state and maintain structural stability in aqueous solution. While the biocompatibility on HeLa cells is demonstrated, the polymer-shielded multifunctional nanoplatform shows both the combined magnetic resonance imaging and redox-triggered photothermal conversion effect. As a contrast agent, the T1 -weighed relaxivity reaches up to 22.77 mm-1  s-1 . The photothermal conversion of the prepared composites can be aroused by yielding a broad near infrared (NIR) adsorption through on-site reduction of the glutathione that is enriched in the tumor environment. The high efficiency ≈61.0% under the irradiation of 808 nm NIR laser illustrates a distinct treatment capability according to cell counting Kit-8 assay while the obvious inhibition for the growth of tumor cells is observed.

Polyoxometalate-antioxidant peptide assembly materials with NIR-triggered photothermal behaviour and enhanced antibacterial activity.

Herein, a novel photothermal agent based on polyoxometalate clusters and food-borne antioxidant peptides was exploited to overcome the inherent problems of poor photothermal stability of polyoxometalate photothermal materials, which commonly appear in the current stage of development, and the inevitable simultaneous inflammatory responses during the therapeutic process.

Ratio-Controlled Precursors of Anderson-Evans Polyoxometalates: Synthesis, Structural Transformation, and Magnetic and Catalytic Properties of a Series of Triol Ligand-Decorated {M2Mo6} Clusters (M = Cu2+, Co2+, Ni2+, Zn2+).

A series of triol ligand [CH3C(CH2OH)3] covalently decorated polyoxometalates (POMs), which could be ascribed to the primary complexes with structural formulas {M2[Mo2O4(CH3C(CH2O)3)2]3}2- (M = Cu2+, Co2+, Ni2+, Zn2+), have been synthesized in organic solvents. Single-crystal X-ray structural analysis reveals that the synthesized polyanionic clusters are comprised of three {Mo2} units and two divalent transition-metal ions connecting to each other in an alternating style, where all {Mo2} blocks were covalently decorated by two triol ligands in the trans conformation. The 1/3 molar ratio of M/Mo in the prepared complexes was higher than those ratios in typical Anderson-Evans, Wells-Dawson, and Keggin POMs. With a decrease in the M/Mo molar ratio of a Mo-contained reactant to 1/6 and/or the addition of acetic acid to the reaction solution, the primary complexes acting as precursors transformed continuously into the corresponding triol-ligand-decorated Anderson-Evans POMs. Detailed investigations were conducted by using different isopolymolybdates in various solvent environments, and several Anderson-Evans POMs in different triol-ligand-decorated fashions were obtained from the primary complexes. In addition, we also realized the transformation between the Anderson-Evans clusters in different decoration fashions by simply controlling the acidity in solution. Magnetic measurement showed a general property, but the catalytic experiments demonstrated that CoII- and Zn II-containing POMs displayed a higher efficiency for the selective oxidation of thioanisole to sulfoxide.

Charge-Transfer Complex Combining Reduced Cluster with Enhanced Stability for Combined Near-Infrared II Photothermal Therapy.

In the search for materials with enhanced near-infrared (NIR) photothermal properties and capability of providing environment-sensitive therapy, a method that combines isolated components into one nanocomposite is developed. The technique simultaneously involves redox, charge-transfer formation, and ionic complexation. During the polyoxophosphomolybdate (PMo) cluster mixing with biosafe chromogen 3,3',5,5'-tetramethylbenzidine (TMB), the reduced state (rPMo) and the oxidized TMB in the state of charge-transfer complex (cTMB) emerge spontaneously. The two reduced and oxidized components with charges form a stable ionic complex that resists physiology, saline, broad pH, and elevated temperature. Both the rPMo and cTMB contribute to the total sustainable photothermal conversion efficiency of 48.4% in the NIR-II region. The ionic complex exhibits biocompatibility in in vitro cell viability evaluation and is demonstrated to enter tumor cells with sustained photothermal property and complexation stability. Due to the local acidity that triggers further interaction among rPMo clusters, a distinct accumulation of the ionic complex at the tumor position is observed after caudal vein injection. Moreover, a remarkable local NIR-II photothermal image appears. The diminishment of tumor in mice with maintained body weight demonstrates the comprehensive effect of this NIR-II photothermal therapeutic material.

A sustainable luminescence-enhanced tri-assembly of polyoxometalate-peptide-polyamine developed for ultrasensitive spermine determination and discrimination.

A supramolecular strategy with sustainable emission amplification of an environmentally sensitive polyoxometalate, Na9[EuW10O36]·32H2O (EuW10), has been constructed for the Spm determination and discrimination. The EuW10 has no response to Put and other biogenic amine but a sensitive response to Spm (LOD = 0.56 nM) and Spd (LOD = 85.93 nM), respectively. Assembling with a cationic peptide from HPV E6, GL-22, achieved the EuW10/GL-22 assembly, which showed a unique enhanced emission response to Spm and distinguished it from Spd successfully. Furthermore, a synergistic rather than competitive binding of Spm to the EuW10/GL-22 assembly was revealed using FT-IR, and NMR titration spectra, together with DLS and TEM, essentially for the three-component sensing system. Besides, both EuW10 and EuW10/GL-22 assembly were successfully applied to the Spm determination in human urine and serum, suggesting the potential of these sensing approaches in detecting trace amounts of Spm in the clinic. Therefore, the constructed supramolecular assembly can detect the Spm sensitively (LOD = 2.0 nM) and efficiently distinguish it step-wise from other biogenic amines. It is a facile, straightforward, sensitive, and selective strategy for Spm determination and discrimination, which will be helpful in addressing the related biological and clinical requirements.

Mo154 Synergistically Enhanced Antibiofilm and Antibacterial Effects of Spermine via Coassembly.

Nowadays, the over use of antibiotics has led to the production of biofilms, which cause antimicrobial treatment to fail and thus are a severe threat to public health globally. Therefore, exploiting antibiofilm agents is highly urgent. In the present study, we report an assembly that is rationally constructed by biogenic amine spermine (Spm) and molybdenum (Mo)-containing polyoxometalate clusters (Mo154), which present efficient antibiofilm and bactericidal effects. On the one hand, the assembly of Mo154/Spm produces large aggregates, which favors 808 nm absorption and exhibits an improved photothermal transition (PTT) under near-infrared (NIR) irradiation. On the other hand, the assembly with Spm enhanced Mo154 uptake to both the biofilm and bacteria, which improved both biofilm elimination and antibacterial effects. Therefore, in addition to providing an efficient antibacterial agent of Mo154/Spm assembly, the present study also offers guidance on the future design of hybrid antibacterial assemblies with efficient effects.

Recent advances of polyoxometalates in multi-functional imaging and photothermal therapy.

Polyoxometalates (POMs) as a kind of molecular metal-oxide cluster with precise chemical composition and architecture have been demonstrated to show potential in multidisciplinary materials. Accompanied by their bioactivities, POM clusters have also been shown to be capable of sensing diseases and allowing synergistic therapy based on their redox and near infrared absorption. In parallel with metal nanoparticles and organic materials, these inorganic clusters have also displayed unique photothermal imaging and therapeutic properties over recent years. In this review, we outlined the main achievements of POMs in the fields of bio-detecting probes and the photothermal effect. Fluorescence detection, magnetic resonance, computed tomography, and photothermal property-supported photoacoustic imaging acting as a multifunction platform that integrates photothermal therapy (PTT) were discussed at the same time. The comparison of nanocomposites to POMs alone in imaging-guided PTT, multi-modal imaging, and the combination of PTT with controlled chemotherapy and gas therapy were described in detail. The advantages and possible drawbacks of POMs as well as perspectives in related areas were analyzed, which ascertained such clusters to be a type of promising agent in biomedical applications.

An ultra-small thermosensitive nanocomposite with a Mo154-core as a comprehensive platform for NIR-triggered photothermal-chemotherapy.

A uniform ultra-small (<10 nm) nanosized dendritic composite was reported for combined photothermal-chemotherapy, wherein a giant ring-like polymolybdate cluster was introduced for the first time as a photothermal therapeutic agent. The giant polyoxometalate cluster possesses strong absorption characteristics in the near infrared region, whereas it has never been applied for biomaterials due to its sensitivity towards environment and structural instability under physiological conditions. Herein, a cationic dendron bearing triethylene glycol monomethyl ether terminal groups was used to cover a giant polyanionic cluster Mo154 surface through a simple electrostatic interaction. Arising from their assembly, the formed core-shell supramolecular composite that has uniform size, precise chemical composition and definite molecular weight not only exhibited mono-dispersion and low cytotoxicity, but also imparted anticancer drug loading and thermoresponsive properties, thus leading to NIR-controlled drug release. When irradiated with an 808 nm NIR laser, the formed complex had significant in vivo photothermal-chemotherapeutic effects on tumor tissue, which makes it a promising material for applications in nanomedicine.