Catalysis-Mediated Male Contraception through Black Phosphorus Nanosheets.

Nanocontraception has been proposed and received extensive attention in recent years for population control. However, currently developed methods for nanocontraception still face problems in efficacy and safety. Here, we propose catalysis-mediated oxidation as a new strategy for nanocontraception. With the catalytic production of highly oxidative species, male contraception was successfully achieved after the administration of black phosphorus nanosheets into the testes of male mice. Further mechanistic studies revealed that contraception was induced by oxidative stress and apoptosis of spermatogenesis cells. Meanwhile, the apoptosis of germ cells released testis antigen and induced immune cell infiltration, which enhanced reproductive damage. Notably, the introduced black phosphorus nanosheets naturally degraded during the catalytic oxidation process and ultimately converted to harmless phosphates, indicating the safety of the strategy. Furthermore, the catalysis-mediated strategy avoids utilizing additional inducers, such as near-infrared irradiation, magnetic fields, or ultrasound, which may cause severe pain. In summary, the proposed catalysis-mediated contraception can be a self-cleared, convenient, and safe strategy for controlling male fertility.

Electrosynthesis of polymer-grade ethylene via acetylene semihydrogenation over undercoordinated Cu nanodots.

The removal of acetylene impurities remains important yet challenging to the ethylene downstream industry. Current thermocatalytic semihydrogenation processes require high temperature and excess hydrogen to guarantee complete acetylene conversion. For this reason, renewable electricity-based electrocatalytic semihydrogenation of acetylene over Cu-based catalysts is an attractive route compared to the energy-intensive thermocatalytic processes. However, active Cu electrocatalysts still face competition from side reactions and often require high overpotentials. Here, we present an undercoordinated Cu nanodots catalyst with an onset potential of -0.15 V versus reversible hydrogen electrode that can exclusively convert C2H2 to C2H4 with a maximum Faradaic efficiency of ~95.9% and high intrinsic activity in excess of -450 mA cm-2 under pure C2H2 flow. Subsequently, we successfully demonstrate simulated crude ethylene purification, continuously producing polymer-grade C2H4 with <1 ppm C2H2 for 130 h at a space velocity of 1.35 × 105 ml gcat-1 h-1. Theoretical calculations and in situ spectroscopies reveal a lower energy barrier for acetylene semihydrogenation over undercoordinated Cu sites than nondefective Cu surface, resulting in the excellent C2H2-to-C2H4 catalytic activity of Cu nanodots.

Missing-Linker-Confined Single-Atomic Pt Nanozymes for Enzymatic Theranostics of Tumor.

Conventional nanozymes often possess low active site density. Pursuing effective strategies for constructing highly active single-atomic nanosystems with maximum atom utilization efficiency is exceptionally attractive. Herein, we develop a facile "missing-linker-confined coordination" strategy to fabricate two self-assembled nanozymes, i.e., conventional nanozyme (NE) and single-atomic nanozyme (SAE), which respectively consist of Pt nanoparticles and single Pt atoms as active catalytic sites anchored in metal-organic frameworks (MOFs) with encapsulated photosensitizers for catalase-mimicking enhanced photodynamic therapy. Compared to a Pt nanoparticle-based conventional nanozyme, a Pt single-atomic nanozyme shows enhanced catalase-mimicking activity in generating oxygen for overcoming tumor hypoxia, thus exhibiting a more efficient reactive oxygen species generation and high tumor inhibition rate.

Tuning the p-Orbital Electron Structure of s-Block Metal Ca Enables a High-Performance Electrocatalyst for Oxygen Reduction.

Most previous efforts are devoted to developing transition metals as electrocatalysts guided by the d-band center model. The metals of the s-block of the periodic table have so far received little attention in the application of oxygen reduction reactions (ORR). Herein, a carbon catalyst with calcium (Ca) single atom coordinated with N and O is reported, which displays exceptional ORR activities in both acidic condition (E1/2  = 0.77 V, 0.1 m HClO4 ) and alkaline condition (E1/2  = 0.90 V, 0.1 m KOH). The CaN, O/C exhibits remarkable performance in zinc-air battery with a maximum power density of 218 mW cm-2 , superior to a series of catalysts reported so far. X-ray absorption near-edge structure (XANES) characterization confirms the formation of N- and O-atom-coordinated Ca in the carbon matrix. Density functional theory (DFT) calculations reveal that the high catalytic activity of main-group Ca is ascribed to the fact that its p-orbital electron structure is regulated by N and O coordination so that the highest peak (EP ) of the projected density of states (PDOS) for the Ca atom is moved close to the Fermi level, thereby facilitating the adsorption of ORR intermediates and electron transfer.

Bioinspired Microenvironment Responsive Nanoprodrug as an Efficient Hydrophobic Drug Self-Delivery System for Cancer Therapy.

Artemisinin compounds have shown satisfactory safety records in anti-malarial clinical practice over decades and have revealed value as inexpensive anti-tumor adjuvant chemotherapeutic drugs. However, the rational design and precise preparation of nanomedicines based on the artemisinin drugs are still limited due to their non-aromatic and fragile chemical structure. Herein, a bioinspired coordination-driven self-assembly strategy was developed to manufacture the artemisinin-based nanoprodrug with a significantly increased drug loading efficacy (∼70 wt %) and decreased preparation complexity compared to conventional nanodrugs. The nanoprodrug has suitable size distribution and robust colloidal stability for cancer targeting in vivo. The nanoprodrug was able to quickly disassemble in the tumor microenvironment with weak acidity and a high glutathione concentration, which guarantees a better tumor inhibitory effect than direct administration and fewer side effects on normal tissues in vivo. This work highlights a new strategy to harness a robust, simplified, organic solvent-free, and highly repeatable route for nanoprodrug manufacturing, which may offer opportunities to develop cost-effective, safe, and clinically available nanomedicines.

Boosting Hydrazine Oxidation Reaction on CoP/Co Mott-Schottky Electrocatalyst through Engineering Active Sites.

The hydrazine oxidation reaction (HzOR), as a substitute for the sluggish oxygen evolution reaction (OER), is identified as a promising powerfrugal strategy for hydrogen production through water splitting. However, the HzOR activity of the present electrocatalysts is unsatisfying because the work potential is much higher than the theoretical value. Herein, we design a typical Mott-Schottky electrocatalyst consisting of CoP/Co nanoparticles for the HzOR, which exhibits remarkable HzOR activity with ultralow potentials of -69 and 177 mV at 10 and 100 mA cm-2, respectively. It stands out in a range of cobalt-based materials and is even comparable to some precious-metal-based materials composed of Pt or Ru. A shown by with structural characterization and density functional theory (DFT) calculations, the interfaces between CoP/Co nanoparticles not only provide the active sites of HzOR but also promote the multistep dehydrogenation reaction of N2H4, thus enhancing the HzOR activity.

Self-Assembled Single-Site Nanozyme for Tumor-Specific Amplified Cascade Enzymatic Therapy.

Nanomaterials with enzyme-mimicking activity (nanozymes) show potential for therapeutic interventions. However, it remains a formidable challenge to selectively kill tumor cells through enzymatic reactions, while leaving normal cells unharmed. Herein, we present a new strategy based on a single-site cascade enzymatic reaction for tumor-specific therapy that avoids off-target toxicity to normal tissues. A copper hexacyanoferrate (Cu-HCF) nanozyme with active single-site copper exhibited cascade enzymatic activity within the tumor microenvironment: Tumor-specific glutathione oxidase activity by the Cu-HCF single-site nanozymes (SSNEs) led to the depletion of intracellular glutathione and the conversion of single-site CuII species into CuI for subsequent amplified peroxidase activity through a Fenton-type Harber-Weiss reaction. In this way, abundant highly toxic hydroxyl radicals were generated for tumor cell apoptosis. The results show that SSNEs could amplify the tumor-killing efficacy of reactive oxygen species and suppress tumor growth in vivo.

Novel ultrasmall multifunctional nanodots for dual-modal MR/NIR-II imaging-guided photothermal therapy.

Encouraging progress in multifunctional nanotheranostic agents that combine photothermal therapy (PTT) and different imaging modalities has been made. However, rational designed and biocompatible multifunctional agents that suitfable for in vivo application is highly desired but still challenging. In this work, we rationally designed novel ultrasmall multifunctional nanodots (FS-GdNDs) by combining the bovine serum albumin (BSA)-based gadolinium oxide nanodots (GdNDs) obtained through a biomineralization process with a small-molecule NIR-II fluorophore (FS). The as-prepared FS-GdNDs with an ultrasmall hydrodynamic diameter of 9.3 nm exhibited prominent NIR-II fluorescence properties, high longitudinal relaxivity (10.11 mM-1 s-1), and outstanding photothermal conversion efficiency (43.99%) and photothermal stability. In vivo studies showed that the FS-GdNDs with enhanced multifunctional characteristics diaplayed satisfactory dual-modal MR/NIR-II imaging performance with a quite low dose. The imaging-guided PTT achieved successful ablation of tumors and effectively extended the survival of mice. Cytotoxicity studies and histological assay demonstrated excellent biocompatibility of the nanodots. Importantly, this novel FS-GdNDs can undergo efficient body clearance through both hepatobiliary and renal excretion pathways. The novel ultrasmall multifunctional FS-GdNDs with excellent features hold tremendous potential in biomedical and clinical applications.

Turning main-group element magnesium into a highly active electrocatalyst for oxygen reduction reaction.

It is known that the main-group metals and their related materials show poor catalytic activity due to a broadened single resonance derived from the interaction of valence orbitals of adsorbates with the broad sp-band of main-group metals. However, Mg cofactors existing in enzymes are extremely active in biochemical reactions. Our density function theory calculations reveal that the catalytic activity of the main-group metals (Mg, Al and Ca) in oxygen reduction reaction is severely hampered by the tight-bonding of active centers with hydroxyl group intermediate, while the Mg atom coordinated to two nitrogen atoms has the near-optimal adsorption strength with intermediate oxygen species by the rise of p-band center position compared to other coordination environments. We experimentally demonstrate that the atomically dispersed Mg cofactors incorporated within graphene framework exhibits a strikingly high half-wave potential of 910 mV in alkaline media, turning a s/p-band metal into a highly active electrocatalyst.

Biomineralization-inspired nanozyme for single-wavelength laser activated photothermal-photodynamic synergistic treatment against hypoxic tumors.

Hypoxia, one of the features of most solid tumors, can severely impede the efficiency of oxygen-dependent treatments such as chemotherapy, radiotherapy and type-II photodynamic therapy. Herein, a catalase-like nanozyme RuO2@BSA (RB) was first prepared through a biomineralization strategy, and a high efficiency near-infrared photosensitizer (IR-808-Br2) was further loaded into the protein shell to generate the safe and versatile RuO2@BSA@IR-808-Br2 (RBIR) for the imaging-guided enhanced phototherapy against hypoxic tumors. RB not only acts like a catalase, but also serves as a photothermal agent that speeds up the oxygen supply under near-infrared irradiation (808 nm). The loaded NIR photosensitizer could immediately convert molecular oxygen (O2) to cytotoxic singlet oxygen (1O2) upon the same laser irradiation. Results indicated that RBIR achieved enhanced therapeutic outcomes with negligible side effects. Features such as a simple synthetic route and imaging-guided and single-wavelength-excited phototherapy make the nanozyme a promising agent for clinical applications.

Dual Graphitic-N Doping in a Six-Membered C-Ring of Graphene-Analogous Particles Enables an Efficient Electrocatalyst for the Hydrogen Evolution Reaction.

Graphene-based materials still exhibit poor electrocatalytic activities for the hydrogen evolution reaction (HER) although they are considered to be the most promising electrocatalysts. We fabricated a graphene-analogous material displaying exceptional activity towards the HER under acidic conditions with an overpotential (57 mV at 10 mA cm-2 ) and Tafel slope (44.6 mV dec-1 ) superior to previously reported graphene-based materials, and even comparable to the state-of-the art Pt/C catalyst. X-ray absorption near-edge structure (XANES) and solid-state NMR studies reveal that the distinct feature of its structure is dual graphitic-N doping in a six-membered carbon ring. Density functional theory (DFT) calculations show that the unique doped structure is beneficial for the activation of C-H bonds and to make the carbon atom bonded to two graphitic N atoms an active site for the HER.

A Mesoporous Nanoenzyme Derived from Metal-Organic Frameworks with Endogenous Oxygen Generation to Alleviate Tumor Hypoxia for Significantly Enhanced Photodynamic Therapy.

Tumor hypoxia compromises the therapeutic efficiency of photodynamic therapy (PDT) as the local oxygen concentration plays an important role in the generation of cytotoxic singlet oxygen (1 O2 ). Herein, a versatile mesoporous nanoenzyme (NE) derived from metal-organic frameworks (MOFs) is presented for in situ generation of endogenous O2 to enhance the PDT efficacy under bioimaging guidance. The mesoporous NE is constructed by first coating a manganese-based MOFs with mesoporous silica, followed by a facile annealing process under the ambient atmosphere. After removing the mesoporous silica shell and post-modifying with polydopamine and poly(ethylene glycol) for improving the biocompatibility, the obtained mesoporous NE is loaded with chlorin e6 (Ce6), a commonly used photosensitizer in PDT, with a high loading capacity. Upon the O2 generation through the catalytic reaction between the catalytic amount NE and the endogenous H2 O2 , the hypoxic tumor microenvironment is relieved. Thus, Ce6-loaded NE serves as a H2 O2 -activated oxygen supplier to increase the local O2 concentration for significantly enhanced antitumor PDT efficacy in vitro and in vivo. In addition, the NE also shows T2 -weighted magnetic resonance imaging ability for its in vivo tracking. This work presents an interesting biomedical use of MOF-derived mesoporous NE as a multifunctional theranostic agent in cancer therapy.

Polypeptide-Conjugated Second Near-Infrared Organic Fluorophore for Image-Guided Photothermal Therapy.

Image-guided photothermal therapy (PTT) is an attractive strategy to improve the diagnosis accuracy and treatment outcomes by monitoring the accumulation of photothermal agents in tumors in real-time and determining the best treatment window. Taking advantage of the superior imaging quality of NIR-II fluorescence imaging and remote-controllable phototherapy modality of PTT, we developed a facile macromolecular fluorophore (PF) by conjugating a small-molecule NIR-II fluorophore (Flav7) with an amphiphilic polypeptide. The PF can form uniform micelles in aqueous solution, which exhibit a slight negative charge. In vitro experimental results showed that the PF nanoparticles showed satisfactory photophysical properties, prominent photothermal conversion efficiency (42.3%), excellent photothermal stability, negligible cytotoxicity, and photothermal toxicity. Meanwhile, the PF can visualize and feature the tumors by NIR-II fluorescence imaging owing to prolonged blood circulation time and enhanced accumulation in tumors. Moreover, in vivo studies revealed that the PF nanoparticles achieved an excellent photothermal ablation effect on tumors with a low dose of NIR-II dye and light irradiation, and the process can be traced by NIR fluorescence imaging.

Ultra-small Albumin Templated Gd/Ru Composite Nanodots for In Vivo Dual modal MR/Thermal Imaging Guided Photothermal Therapy.

Multifunctional theranostic nanoagents which realize precise diagnosis and treatment of tumors are attracting increasing interests in recent years. However, efficient and controlled synthesis of ultra-small noble metal nanoagents remains a challenge. Here, monodisperse Gd/Ru@BSA nanodots (GRBNDs) are successfully fabricated via a totally "green", "one-pot" protocol for in situ reduction of Ru(III) and biomineralization of Gd(III) in the presence of albumin. The as-prepared nanoagent possesses the features of being ultra small in size (≈6.7 nm), having strong colloidal stability, and thermal stability as well as high photothermal conversion efficiency (η = 50.7%). As expected, the GRBNDs achieve a significant efficacy of anticancer therapy under LASER activation both in vitro and in vivo. It also exhibits superior T1 -weighted magnetic resonance (MR) imaging ability due to its high longitudinal relaxivity value (r1 = 10.98 × 10-3 m-1 s-1 ). Moreover, it is demonstrated to be renal clearable with negligible systemic toxicity. This work highlights a straightforward and repeatable approach for synthesizing highly effective and multifunctional noble metal nanoagent of great clinical promising for cancer theranostics.

Ultrasmall Ru/Cu-doped RuO2 Complex Embedded in Amorphous Carbon Skeleton as Highly Active Bifunctional Electrocatalysts for Overall Water Splitting.

Developing highly active electrocatalysts with superior durability for both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in the same electrolyte is a grand challenge to realize the practical application of electrolysis water for producing hydrogen. In this work, an ultrasmall Ru/Cu-doped RuO2 complex embedded in an amorphous carbon skeleton is synthesized, through thermolysis of Ru-modified Cu-1,3,5-benzenetricarboxylic acid (BTC), as a highly efficient bifunctional catalyst for overall water splitting electrocatalysis. The ultrasmall Ru nanoparticles in the complex expose more activity sites for hydrogen evolution and outperform the commercial Pt/C. Meanwhile, the ultrasmall RuO2 nanoparticles exhibit superior oxygen evolution performance over commercial RuO2, and the doping of Cu into the ultrasmall RuO2 nanoparticles further enhances the oxygen evolution performance of the catalyst. The outstanding OER and decent HER catalytic activity endow the complex with impressive overall water splitting performance superior to that of the state-of-the-art electrocatalysts, which just require 1.47 and 1.67 V to achieve a current density of 10 mA cm-2 and 100 mA cm-2. The density functional theory calculations reveal that a Cu dopant could effectively tailor the d-band center, thereby tuning electronic structure of Ru activity sites on the RuO2 (110) plane and ultimately improving the OER performance of RuO2.

Photo-Enhanced Singlet Oxygen Generation of Prussian Blue-Based Nanocatalyst for Augmented Photodynamic Therapy.

Therapeutic effects of photodynamic therapy (PDT) remain largely limited because of tumor hypoxia. Herein, we report safe and versatile nanocatalysts (NCs) for endogenous oxygen generation and imaging-guided enhanced PDT. The NCs (named as PSP) are prepared by coating Prussian blue (PB) with mesoporous silica to load photosensitizer (zinc phthalocyanine, ZnPc), followed by the modification of polyethylene glycol chains. The inner PB not only acts like a catalase for hydrogen peroxide decomposition but also serves as a photothermal agent to increase the local temperature and then speed up the oxygen supply under near-infrared irradiation. The loaded ZnPc can immediately transform the formed oxygen to generate cytotoxic singlet oxygen upon the same laser irradiation due to the overlapped absorption between PB and ZnPc. Results indicate that the PSP-ZnPc (PSPZP) NCs could realize the photothermally controlled improvement of hypoxic condition in cancer cells and tumor tissues, therefore demonstrating enhanced cancer therapy by the incorporation of PDT and photothermal therapy.

In Situ One-Pot Synthesis of MOF-Polydopamine Hybrid Nanogels with Enhanced Photothermal Effect for Targeted Cancer Therapy.

Herein, a simple one-pot way is designed to prepare a type of multifunctional metal-organic framework (MOF)-based hybrid nanogels by in situ hybridization of dopamine monomer in the skeleton of MnCo. The resultant hybrid nanoparticles (named as MCP) show enhanced photothermal conversion efficiency in comparison with pure polydopamine or MnCo nanoparticles (NPs) synthesized under a similar method and, therefore, show great potential for photothermal therapy (PTT) in vivo. The MCP NPs are expected to possess T1 positive magnetic resonance imaging ability due to the high-spin Mn-N6 (S = 5/2) in the skeleton of MnCo. To improve the therapy efficiency as a PTT agent, the MCP NPs are further modified with functional polyethylene glycol (PEG) and thiol terminal cyclic arginine-glycine-aspartic acid peptide, respectively: the first one is to increase the stability, biocompatibility, and blood circulation time of MCP NPs in vivo; the second one is to increase the tumor accumulation of MCP-PEG NPs and improve their therapeutic efficiency as photothermal agent.

Novel Metal Polyphenol Framework for MR Imaging-Guided Photothermal Therapy.

Phothermal therapy has received increasing attention in recent years as a potentially effective way to treat cancer. In pursuit of a more biocompatible photothermal agent, we utilize biosafe materials including ellagic acid (EA), polyvinylpyrrolidone (PVP), and iron element as building blocks, and we successfully fabricate a homogeneous nanosized Fe-EA framework for the first time by a facile method. As expected, the novel nanoagent exhibits no obvious cytotoxicity and good hemocompatibility in vitro and in vivo. The microenvironment responsiveness to both pH and hydrogen peroxide makes the NPs biodegradable in tumor tissues, and the framework should be easily cleared by the body. Photothermal potentials of the nanoparticles are demonstrated with relevant features of strong NIR light absorption, moderately effective photothermal conversion efficiency, and good photothermal stability. The in vivo photothermal therapy also achieved effective tumor ablation with no apparent toxicity. On the other hand, it also exhibits T2 MR imaging ability originated from ferric ions. Our work highlights the promise of the Fe-EA framework for imaging-guided photothermal therapy.

Core-Shell Structurized Fe3O4@C@MnO2 Nanoparticles as pH Responsive T1-T2* Dual-Modal Contrast Agents for Tumor Diagnosis.

Biocompatible core-shell Fe3O4@C@MnO2 nanoparticles (named as FOCMO NPs) with an average size at 130 nm prepared through an effortless yet efficient strategy were employed as pH-activatable T1-T2* dual-modality magnetic resonance imaging (MRI) contrast agents (CAs). The release rate of Mn ions in acidic PBS (pH = 5.0) was approximately 10 times to that under condition with pH value of 7.4. Benefiting from excellent acid responsiveness, which facilitates the release of ions from FOCMO NPs at tumor region with acidic microenvironment and organelles, the diagnosis accuracy was commendably improved. After intravenous injection of FOCMO NPs, an efficiently intensive contrast in tumors are realized with a distinct enhancement of 127% in T1 MRI signal 24 h after the administration. Moreover, a significant decreasement of 71% is witnessed in T2 MRI signal. Those demonstrated that FOCMO NPs can achieve the purpose of positive/negative MRI simultaneously. Furthermore, obtained FOCMO NPs showed great hemocompatibility and negligible toxicity.

Bimetallic Zeolitic Imidazolate Framework as an Intrinsic Two-Photon Fluorescence and pH-Responsive MR Imaging Agent.

Zeolitic imidazolate framework-8 (ZIF-8) has received wide attention in recent years as a potential drug vehicle for the treatment of cancer due to its acid-responsiveness and moderate biocompatibility. However, its congenital deficiency of intrinsic imaging capability limits its wider applications; therefore, a postsynthetic exchange approach was utilized to introduce paramagnetic manganese(II) ions into the ZIF-8 matrix. As a result, bimetallic zeolitic imidazolate frameworks (Mn-Zn-ZIF) were thus fabricated and exhibited pH-responsive T1-weighted magnetic resonance imaging (MRI) contrast effect. Remarkably, we also found its own fluorescence derived from 2-methylimidazole, which is the first report of the intrinsic two-photon fluorescence imaging of ZIFs to our knowledge. Mn-Zn-ZIF still preserves the original properties of ZIF-8 of high surface areas, microporosity, and acid sensitivity. After further PEGylation of Mn-Zn-ZIF, the nanoparticles showed no obvious toxicity and its MRI contrast effect has also been enhanced. Our work highlights the promise of modified zeolitic imidazolate frameworks as potential cancer theranostic platforms.