Nanoplatform-based cellular reactive oxygen species regulation for enhanced oncotherapy and tumor resistance alleviation

The cancer cells realize their proliferation and metastasis activities based on the special redox adaptation to increased reactive oxygen species(ROS) level, which inversely makes them sensitive to external interference with their redox state. In view of this, in recent decades, researchers have made great efforts to construct a series of novel nanoplatform-based ROS-mediated cancer therapies through increasing ROS generation and inhibiting the ROS elimination. Besides, the multidrug resistance ...     

Effective Cancer Cell Killing by Hydrophobic Nanovoid‐Enhanced Cavitation under Safe Low‐Energy Ultrasound

β‐Cyclodextrin (β‐CD)‐capped mesoporous silica nanoparticles with hydrophobic internal nanovoids were prepared and used for effective cancer cell killing in synergistic combination with low‐energy ultrasound (≤1.0 W cm^?2, 1 MHz). The water‐dispersible nanoparticles with hydrophobic internal nanovoids can be taken up by cancer cells and subsequently evoke a remarkable cavitation effect under irradiation with mild low‐energy ultrasound (≤1.0 W cm^?2, 1 MHz). A significant cancer cell killing effect was observed in cancer cells and in a mouse xenograft tumor model treated with the nanoagents together with the low‐energy ultrasound, showing a distinct dependence on the concentration of nanoagents and ultrasound intensity. By contrast, an antitumor effect was not observed when either low‐energy ultrasound or nanoagents were applied alone. These findings are significant as the technique promises a safe, low‐cost, and effective treatment for cancer therapy.     

The Role of Interface on the Properties of Cluster Assemblies

Atomic clusters characterized by finite size, low dimensionality, and reduced coordination number exhibit many novel properties that are very different from their bulk. As these clusters are assembled, their properties can be significantly altered due to the interaction of these clusters with each other as well as with their support. This paper provides a brief review of the cluster properties that are affected when clusters are deposited on metallic or organic substrates, isolated in matrices or in zeolite cages, coated with acetate ligands, or simply allowed to self-assemble without the presence of any reactive species. It is shown that the interface between the clusters and their support can play an important role on the properties of clusters as their unique characteristics do.     

Lessons from the past and charting the future of marine natural products drug discovery and chemical biology

Marine life forms are an important source of structurally diverse and biologically active secondary metabolites, several of which have inspired the development of new classes of therapeutic agents. These success stories have had to overcome difficulties inherent to natural products-derived drugs, such as adequate sourcing of the agent and issues related to structural complexity. Nevertheless, several marine-derived agents are now approved, most as "first-in-class" drugs, with five of seven appearing in the past few years. Additionally, there is a rich pipeline of clinical and preclinical marine compounds to suggest their continued application in human medicine. Understanding of how these agents are biosynthetically assembled has accelerated in recent years, especially through interdisciplinary approaches, and innovative manipulations and re-engineering of some of these gene clusters are yielding novel agents of enhanced pharmaceutical properties compared with the natural product.     

Scanning tunneling microscopy studies of metal clusters supported on TiO2 (110): Morphology and electronic structure

A brief review of our laboratory's recent scanning tunneling microscopy (STM) studies on nanoclusters supported on TiO₂(110) is presented. Particular emphasis is placed on the system Au/TiO₂(110). The nucleation and growth of the clusters, which were vapor-deposited on TiO₂(110) under ultra high vacuum (UHV) conditions, were investigated using STM. It was found that Au, Pd, and Ag clusters all grow in a three-dimensional (3D) (Volmer-Weber) fashion on TiO₂(110), but that at low coverages, quasi-two dimensional (quasi-2D) Au and Pd clusters were observed. These quasi-2D clusters are characterized by heights of 1–2 atomic layers. Annealing studies show that Au and Pd clusters form large microcrystals with well-defined hexagonal shapes. Al clusters, which have a strong interaction with the substrate, are oxidized upon deposition, “wetting” the surface and forming small clusters. In addition to the topographic studies, the local electronic properties of these clusters have been studied using scanning tunneling spectroscopy (STS) to measure the cluster band gaps. The electronic structure was found to be cluster size-dependent, as seen by the appearance of a band gap as the cluster size decreased. More specifically, the onset of cluster metallic properties correlates with the transition from quasi-2D to 3D cluster growth.     

Novel multifunctional theranostic nanoagents based on Ho3+ for CT/MRI dual-modality imaging-guided photothermal therapy

Because of the intrinsic defects of traditional treatment of cancer,it is quite needed to construct novel theranostic nanoagents that can not only improve the accuracy of imaging diagnosis but also achieve highly efficient therapy of cancer.Herein,we fabricated polydopamine-functionalized ammonium holmium fluoride nanocomposites(AHF@PDA)for dual-modality bioimaging(magnetic resonance imaging(MRI)and computed tomography(CT))owing to the high X-ray attenuation feature and magnetic property of Ho³⁺.Moreover,PDA shell endows AHF@PDA with excellent photothermal conversion performances and robust biocompatibility,leading to good treatment effect in vitro and in vivo.All above positive results certify that AHF@PDA have good potential as theranostic agents for clinical application in the future.     

Grafted semiconducting polymer amphiphiles for multimodal optical imaging and combination phototherapy

Semiconducting polymer nanoparticles (SPNs) have gained growing attention in biomedical applications. However, the preparation of SPNs is usually limited to nanoprecipitation in the presence of amphiphilic copolymers, which encounters the issue of dissociation. As an alternative to SPNs, grafted semiconducting polymer amphiphiles (SPAs) composed of a semiconducting polymer (SP) backbone and hydrophilic side chains show increased physiological stability and improved optical properties. This review summarizes recent advances in SPAs for cancer imaging and combination phototherapy. The applications of SPAs in optical imaging including fluorescence, photoacoustic, multimodal and activatable imaging are first described, followed by the discussion of applications in imaging-guided phototherapy and combination therapy, light-triggered drug delivery and gene regulation. At last, the conclusion and future prospects in this field are discussed.

This review summarizes the applications of grafted semiconducting polymer amphiphiles (SPAs) as multimodal optical nanoagents for cancer imaging and combination phototherapy.     

Reactivities and biological functions of iron-sulfur clusters

Iron-sulfur clusters are prevalent in biological systems. Through studies of iron-sulfur proteins and synthetic model clusters, it was realized early on that these clusters functioned as facile electron transfer agents. Until recently it was widely thought that they served exclusively in that capacity. However, in the last decade, it has become clear that their reactivities and biological functions are much more diverse. It is now apparent that these clusters can serve as the active sites of enzymes, as well as in the regulation of enzymatic activity. Synthetic clusters, which have been shown to undergo a variety of core rearrangements or structural changes, have provided insight into possible mechanisms of cluster formation or activity regulation in enzymes. Rigid tripodal ligands have been constructed which capture synthetic iron-sulfur clusters in a cavity which permits controlled reactivity studies. In this article, we review these recent developments and suggest some future directions the field may take.     

Synergetic Effect of Mo6 Clusters and Gold Nanoparticles on the Photophysical Properties of Both Components

Photodynamic and photothermal therapies (PDT, and PTT, respectively) are promising candidates for multimodal anticancer therapies (i.e., combinations of therapies), since their action is based on mechanisms that generally cannot be resisted by cancer cells, that is, generation of highly oxidizing oxygen species and high temperature, respectively. Herein, hybrid materials that combine octahedral molybdenum clusters as potential PDT agents and plasmonic spherical gold nanoparticles (AuNPs) as PTT agents are reported. Partial overlap of the photoemission spectrum of the cluster and the surface plasmon resonance band of the AuNPs facilitates energy transfer between the photoactive components, which resulted in synergetic enhancement of their photophysical properties. Specifically, by careful selection of the spacing between the cluster and the gold nanoparticle, a significant increase in luminescence and photosensitizing properties of the cluster was achieved in comparison with similar, but gold-free, particles. On the other hand, the cluster complex facilitated energy conversion to heat by gold particles and hence increased the heating rate under laser irradiation.     

Two-Dimensional Nanomaterials for Photothermal Therapy

Two-dimensional (2D) nanomaterials are currently explored as novel photothermal agents because of their ultrathin structure, high specific surface area, and unique optoelectronic properties. In addition to single photothermal therapy (PTT), 2D nanomaterials have demonstrated significant potential in PTT-based synergistic therapies. In this Minireview, we summarize the recent progress in 2D nanomaterials for enhanced photothermal cancer therapy over the last five years. Their unique optical properties, typical synthesis methods, and surface modification are also covered. Emphasis is placed on their PTT and PTT-synergized chemotherapy, photodynamic therapy, and immunotherapy. The major challenges of 2D photothermal agents are addressed and the promising prospects are also presented.     

Directed synthesis of stable large polyoxomolybdate spheres

Polyoxometalates or POMs, a class of inorganic transition metal-oxide based clusters, have gained significant interest owing to their catalytic, magnetic, and material science applications. All such applications require high surface area POM based materials. However, chemically synthesized POMs are still at most in the range of a few nanometers, with their size and morphology being difficult to control. Hence, there is an immediate need to develop design principles that allow easy control of POM morphology and size on mesoscopic (50-500 nm) length scales. Here, we report a design strategy to meet this need. Our method reported here avoids a complex chemical labyrinth by using a prefabricated cationic 1,2-dioleol-3-trimethylammonium-propane (DOTAP) vesicle as a scaffold/structure directing agent and gluing simple anionic heptamolybdates by electrostatic interaction and hydrogen bonds to form large POM spheres. By this method, complexity in the resulting structure can be deliberately induced either via the scaffold or via the oxometalate. The high degree of control in the matter of the size and morphology of the resulting POM superstructures renders this method attractive from a synthetic standpoint.     

DFT study on the five isomers of PW(12)O(40)(3)(-): relative stabilization upon reduction

The electronic characteristics and the redox properties of each isomer of PW(12)O(40)(3)(-) depend on the arrangement adopted by the metal-oxide framework. At the DFT/BP86 level, we computed the structures of the five isomers of PW(12)O(40)(3)(-) in oxidized form. The energy scale fits the experimental findings as well as the number of rotated triads of the metal-oxide core since the energy grows as follows: alpha < beta < gamma < delta < epsilon. The reduced clusters behave differently as long as the beta form becomes the most stable isomer after the second reduction. The gamma isomer also gains stability upon reduction, but not enough to be competitive with beta. For the 4-fold reduced PW(12) cluster, the energy difference computed between beta and gamma in solution is 11 kcal mol(-)(1). This large difference proves that the beta --> gamma isomerization is not favored upon simple reduction. The other isomers, delta and epsilon, are much more unstable than alpha or beta in any reduction state.     

Two‐Dimensional Nanomaterials for Photothermal Therapy

Two‐dimensional (2D) nanomaterials are currently explored as novel photothermal agents because of their ultrathin structure, high specific surface area, and unique optoelectronic properties. In addition to single photothermal therapy (PTT), 2D nanomaterials have demonstrated significant potential in PTT‐based synergistic therapies. In this Minireview, we summarize the recent progress in 2D nanomaterials for enhanced photothermal cancer therapy over the last five years. Their unique optical properties, typical synthesis methods, and surface modification are also covered. Emphasis is placed on their PTT and PTT‐synergized chemotherapy, photodynamic therapy, and immunotherapy. The major challenges of 2D photothermal agents are addressed and the promising prospects are also presented.     

Synthesis, structure and properties of metal nanoclusters

Metal nanoclusters have physical properties differing significantly from their bulk counterparts. Metallic properties such as delocalization of electrons in bulk metals which imbue them with high electrical and thermal conductivity, light reflectivity and mechanical ductility may be wholly or partially absent in metal nanoclusters, while new properties develop. We review modern synthetic methods used to form metal nanoclusters. The focus of this critical review is solution based chemical synthesis methods which produce fully dispersed clusters. Control of cluster size and surface chemistry using inverse micelles is emphasized. Two classes of metals are discussed, transition metals such as Au and Pt, and base metals such as Co, Fe and Ni. The optical and catalytic properties of the former are discussed and the magnetic properties of the latter are given as examples of unexpected new size-dependent properties of nanoclusters. We show how classical surface science methods of characterization augmented by chemical analysis methods such as liquid chromatography can be used to provide feedback for improvements in synthetic protocols. Characterization of metal clusters by their optical, catalytic, or magnetic behavior also provides insights leading to improvements in synthetic methods. The collective physical properties of closely interacting clusters are reviewed followed by speculation on future technical applications of clusters. (125 references).     

Sub-nanometre sized metal clusters: from synthetic challenges to the unique property discoveries

Sub-nanometre sized metal clusters, with dimensions between metal atoms and nanoparticles, have attracted more and more attention due to their unique electronic structures and the subsequent unusual physical and chemical properties. However, the tiny size of the metal clusters brings the difficulty of their synthesis compared to the easier preparation of large nanoparticles. Up to now various synthetic techniques and routes have been successfully applied to the preparation of sub-nanometre clusters. Among the metals, gold clusters, especially the alkanethiolate monolayer protected clusters (MPCs), have been extensively investigated during the past decades. In recent years, silver and copper nanoclusters have also attracted enormous interest mainly due to their excellent photoluminescent properties. Meanwhile, more structural characteristics, particular optical, catalytic, electronic and magnetic properties and the related technical applications of the metal nanoclusters have been discovered in recent years. In this critical review, recent advances in sub-nanometre sized metal clusters (Au, Ag, Cu, etc.) including the synthetic techniques, structural characterizations, novel physical, chemical and optical properties and their potential applications are discussed in detail. We finally give a brief outlook on the future development of metal nanoclusters from the viewpoint of controlled synthesis and their potential applications.     

Structure and function of oxide nanostructures: catalytic consequences of size and composition

Redox and acid-base properties of dispersed oxide nanostructures change markedly as their local structure and electronic properties vary with domain size. These changes give rise to catalytic behavior, site structures, and reaction chemistries often unavailable on bulk crystalline oxides. Turnover rates for redox and acid catalysis vary as oxide domains evolve from isolated monomers to two-dimensional oligomers, and ultimately into clusters with bulk-like properties. These reactivity changes reflect the ability of oxide domains to accept or redistribute electron density in kinetically-relevant reduction steps, in the formation of temporary acid sites via reductive processes, and in the stabilization of cationic transition states. Reduction steps are favored by low-lying empty orbitals prevalent in larger clusters, which also favor electron delocalization, stable anions, and strong Br?nsted acidity. Isomerization of xylenes and alkanes, elimination reactions of alkanols, and oxidation of alkanes to alkenes on V, Mo, Nb, and W oxide domains are used here to demonstrate the remarkable catalytic diversity made available by changes in domain size. The reactive and disordered nature of small catalytic domains introduces significant challenges in their synthesis and their structural and mechanistic characterization, which require in situ probes and detailed kinetic analysis. The local structure and electronic properties of these materials must be probed during catalysis and their catalytic function be related to specific kinetically-relevant steps. Structural uniformity can be imposed on oxide clusters by the use of polyoxometalate clusters with thermodynamically stable and well-defined size and connectivity. These clusters provide the compositional diversity and the structural fidelity required to develop composition-function relations from synergistic use of experiments and theory. In these clusters, the valence and electronegativity of the central atom affects the acid strength of the polyoxometalate clusters and the rate constants for acid catalyzed elementary steps via the specific stabilization of cationic transition states in isomerization and elimination reactions.     

Optical properties of large molecules and clusters in the frenkel exciton picture

Frenkel exciton theory is reviewed. This theory yields general formulas relating the absorption and circular dichroism spectra of large molecules or clusters to the optical properties of their subunits. It is shown that for weakly interacting systems, the circular dichroism associated with a band of exciton states is proportional to tr( FH ), where F is an “optical matrix” constructed from the positions and transition dipole moments of the subunits, and H is an interaction-energy matrix. It is shown that if a system expnds isotropically, then tr( FH ) falls off as the inverse square of the linear dimensions. This result is compared with experimental measurements of the low-temperature optical rotatory dispersion of proteins as a function of temperature. The optical properties of helical polymers are also discussed as a function of their geometrical parameters.     

Bile Acid Conjugates with Anticancer Activity: Most Recent Research

The advantages of a treatment modality that combines two or more therapeutic agents in cancer therapy encourages the study of hybrid functional compounds for pharmacological applications. In light of this, we reviewed recent works on hybrid molecules based on bile acids. Due to their biological properties, as well as their different chemical/biochemical reactive moieties, bile acids can be considered very interesting starting molecules for conjugation with natural or synthetic bioactive molecules.     

金属-有机框架材料在癌症诊疗中的应用

成像技术的迅速发展使科学家和临床医生能够准确地了解癌症的发病机制和病理过程, 并根据患者的情况制定个性化的治疗策略. 将各种成像与治疗试剂整合为一体的癌症诊疗平台, 可以同时用于癌症的诊断和治疗, 受到了广泛的关注. 金属-有机框架材料(MOFs)是由有机配体和金属离子/离子簇自组装而成的一种有趣而独特的多孔有机-无机杂化材料. 由于其易于后修饰、 孔隙和结构可设计、 功能可调等特点, 已被证明具有成为癌症诊疗药物负载平台的巨大潜力. 本文介绍了将诊疗药物负载到MOFs中的策略, 并综合评述了在磁共振成像、 计算机断层扫描成像、 正电子发射断层扫描成像、 光学成像和光声成像等多种成像技术指导下, MOFs作为癌症诊断和治疗平台的发展概况. 此外, 还讨论了MOFs在癌症诊疗和临床转化方面当前面临的挑战和发展前景.