Facile Synthesis of Fe3O4@Au/PPy-DOX Nanoplatform with Enhanced Glutathione Depletion and Controllable Drug Delivery for Enhanced Cancer Therapeutic Efficacy

The complex physiological environment and inherent self-healing function of tumors make it difficult to eliminate malignant tumors by single therapy. In order to enhance the efficacy of antitumor therapy, it is significant and challenging to realize multi-mode combination therapy by utilizing/improving the adverse factors of the tumor microenvironment (TME). In this study, a novel Fe₃O₄@Au/PPy nanoplatform loaded with a chemotherapy drug (DOX) and responsive to TME, near-infrared (NIR) laser and magnetic field was designed for the combination enhancement of eliminating the tumor. The Fe²⁺ released at the low pH in TME can react with endogenous H₂O₂ to induce toxic hydroxyl radicals (·OH) for chemodynamic therapy (CDT). At the same time, the generated Fe³⁺ could deplete overexpressed glutathione (GSH) at the tumor site to prevent reactive oxygen species (ROS) from being restored while producing Fe²⁺ for CDT. The designed Fe₃O₄@Au/PPy nanoplatform had high photothermal (PT) conversion efficiency and photodynamic therapy (PDT) performance under NIR light excitation, which can promote CDT efficiency and produce more toxic ROS. To maximize the cancer-killing efficiency, the nanoplatform can be successfully loaded with the chemotherapeutic drug DOX, which can be efficiently released under NIR excitation and induction of slight acidity at the tumor site. In addition, the nanoplatform also possessed high saturation magnetization (20 emu/g), indicating a potential magnetic targeting function. In vivo and in vitro results identified that the Fe₃O₄@Au/PPy-DOX nanoplatform had good biocompatibility and magnetic-targeted synergetic CDT/PDT/PTT/chemotherapy antitumor effects, which were much better than those of the corresponding mono/bi/tri-therapies. This work provides a new approach for designing intelligent TME-mediated nanoplatforms for synergistically enhancing tumor therapy.     

A Light-Responsive Injectable Hydrogel with Remodeling Tumor Microenvironment for Light-Activated Chemodynamic Therapy

Chemodynamic therapy (CDT) based on Fenton-like reaction is often limited by the tumor microenvironment (TME), which has insufficient hydrogen peroxide, and single CDT treatment is often less efficacious. To overcome these limitations, a hydrogel-based system is designed to enhance the redox stress (EOH) by loading the composite nanomaterial Cu-Hemin-Au, into the agarose hydrogels. The hydrogels can reach the tumor site upon intratumoral injection, and then coagulate and stay for extended period. Once irradiated with near-infrared light, the Cu-Hemin-Au act as a photothermal agent to convert the light energy into heat, and the EOH gradually heated up and softened, releasing the Cu-Hemin-Au residing in it to achieve photothermal therapy (PTT). Benefiting from the glucose oxidase (GOx)-like activity of the Au nanoparticles, glucose in the tumor cells is largely consumed, and hydrogen peroxide (H₂O₂) is generated in situ, and then Cu-Hemin-Au react with sufficient H₂O₂ to generate a large amount of reactive oxygen species, which promote the complete inhibition of tumor growth in mice during the treatment cycle. The hydrogel system for the synergistic enhancement of oxidative stress achieves good PTT/CDT synergy, providing a novel inspiration for the next generation of hydrogels for application in antitumor therapy.     

NIR‐II Driven Plasmon‐Enhanced Catalysis for a Timely Supply of Oxygen to Overcome Hypoxia‐Induced Radiotherapy Tolerance

Hypoxia, as a characteristic feature of solid tumor, can significantly adversely affect the outcomes of cancer radiotherapy (RT), photodynamic therapy, or chemotherapy. In this study, a strategy is developed to overcome tumor hypoxia‐induced radiotherapy tolerance. Specifically, a novel two‐dimensional Pd@Au bimetallic core–shell nanostructure (TPAN) was employed for the sustainable and robust production of O₂ in long‐term via the catalysis of endogenous H₂O₂. Notably, the catalytic activity of TPAN could be enhanced via surface plasmon resonance (SPR) effect triggered by NIR‐II laser irradiation, to enhance the O₂ production and thereby relieve tumor hypoxia. Thus, TPAN could enhance radiotherapy outcomes by three aspects: 1) NIR‐II laser triggered SPR enhanced the catalysis of TPAN to produce O₂ for relieving tumor hypoxia; 2) high‐Z element effect arising from Au and Pd to capture X‐ray energy within the tumor; and 3) TPAN affording X‐ray, photoacoustic, and NIR‐II laser derived photothermal imaging, for precisely guiding cancer therapy, so as to reduce the side effects from irradiation.     

A GdW10@PDA-CAT Sensitizer with High-Z Effect and Self-Supplied Oxygen for Hypoxic-Tumor Radiotherapy

Anticancer treatment is largely affected by the hypoxic tumor microenvironment (TME), which causes the resistance of the tumor to radiotherapy. Combining radiosensitizer compounds and O₂ self-enriched moieties is an emerging strategy in hypoxic-tumor treatments. Herein, we engineered GdW₁₀@PDA-CAT (K₃Na₄H₂GdW₁₀O₃₆·2H₂O, GdW₁₀, polydopamine, PDA, catalase, CAT) composites as a radiosensitizer for the TME-manipulated enhancement of radiotherapy. In the composites, Gd (Z = 64) and W (Z = 74), as the high Z elements, make X-ray gather in tumor cells, thereby enhancing DNA damage induced by radiation. CAT can convert H₂O₂ to O₂ and H₂O to enhance the X-ray effect under hypoxic TME. CAT and PDA modification enhances the biocompatibility of the composites. Our results showed that GdW₁₀@PDA-CAT composites increased the efficiency of radiotherapy in HT29 cells in culture. This polyoxometalates and O₂ self-supplement composites provide a promising radiosensitizer for the radiotherapy field.     

Biomineralization of Versatile CuS/Gd2O3 Hybrid Nanoparticles for MR Imaging and Antitumor Photothermal Chemotherapy

The versatile application of nanoparticles in integrating imaging and therapy has aroused extensive research interest in precision medicine. Of the various nanoparticles that have been studied, CuS has shown great potential in the construction of multifunctional agents, owing to its excellent photothermal heating properties. Herein, we report a facile one‐pot biomineralization approach for the preparation of versatile bovine‐serum‐albumin‐conjugated CuS/Gd₂O₃ hybrid nanoparticles (BSA?CuS/Gd₂O₃ HNPs), which simultaneously possessed strong longitudinal relaxivity, an outstanding photothermal effect, high drug‐loading capacity, and pH/temperature‐responsive drug release. The versatile nanoparticles were used for magnetic resonance imaging (MRI) and antitumor photothermal chemotherapy, both in vitro and in vivo. In vivo MRI showed that the BSA?CuS/Gd₂O₃ HNPs had a long circulation time and effective passive tumor‐uptake ability. More importantly, combined in vitro and in vivo therapy demonstrated that drug‐loaded BSA?CuS/Gd₂O₃ HNPs offered outstanding synergistic therapeutic efficacy for tumor inhibition.     

A novel H(2)O(2) amperometric biosensor based on gold nanoparticles/self-doped polyaniline nanofibers

A new kind of gold nanoparticles/self-doped polyaniline nanofibers (Au/SPAN) with grooves has been prepared for the immobilization of horseradish peroxidase (HRP) on the surface of glassy carbon electrode (GCE). The ratio of gold in the composite nanofibers was up to 64%, which could promote the conductivity and biocompatibility of SPAN and increase the immobilized amount of HRP molecules greatly. The electrode exhibits enhanced electrocatalytic activity in the reduction of H₂O₂ in the presence of the mediator hydroquinone (HQ). The effects of concentration of HQ, solution pH and the working potential on the current response of the modified electrode toward H₂O₂ were optimized to obtain the maximal sensitivity. The proposed biosensor exhibited a good linear response in the range from 10 to 2000 μM with a detection limit of 1.6 μM (S/N = 3) under the optimum conditions. The response showed Michaelis–Menten behavior at larger H₂O₂ concentrations, and the apparent Michaelis–Menten constant K_m was estimated to be 2.21 mM. The detection of H₂O₂ concentration in real sample showed acceptable accuracy with the traditional potassium permanganate titration.     

Electrochemical synthesis of Fe3O4-PB nanoparticles with core-shell structure and its electrocatalytic reduction toward H2O2

The Fe₃O₄-Prussian blue (PB) nanoparticles with core-shell structure have been in situ prepared directly on a nano-Fe₃O₄-modified glassy carbon electrode by cyclic voltammetry (CV). First, the magnetic nano-Fe₃O₄ particles were synthesized and characterized by X-ray diffraction. Then, the properties of the Fe₃O₄-PB nanoparticles were characterized by CV, electrochemical impedance spectroscopy, and superconducting quantum interference device. The resulting core-shell Fe₃O₄-PB-modified electrode displays a dramatic electrocatalytic ability toward H₂O₂ reduction, and the catalytic current was a linear function with the concentration of H₂O₂ in the range of 1 × 10⁻⁷~5 × 10⁻⁴ mol/l. A detection limit of 2 × 10⁻⁸ (s/n = 3) was determined. Moreover, it showed good reproducibility, enhanced long-term stability, and potential applications in fields of magnetite biosensors.     

A facile one-pot interfacial synthesis of Pt nanoparticles/polypyrrole composites and their application for non-enzymatic sensing hydrogen peroxide

Pt nanoparticles (PtNPs)/polypyrole (PPy) composites were successfully prepared through a facile one-pot interfacial polymerization of pyrrole by using H₂PtCl₆ as the oxidant for the first time. The as-prepared PPy was granular particles with particle size within a few hundred nanometers, on which PtNPs (1.7–3.5) nm were homogeneously dispersed. The PtNPs/PPy composites displayed excellent electrocatalytic activity toward redox of H₂O₂. The non-enzyme sensor constructed with PtNPs/PPy composites displayed good sensing ability toward H₂O₂ at ?0.1 V with a significantly high sensitivity of 6056 μAmM^?1cm^?2 and a low detection limit of 1.8 μM (S/N = 3).     

Fe3O4@SiO2@polymer复合粒子的制备及在药物控制释放中的应用

本文通过多步反应制备了一种新型的、多层结构的、多功能的磁性纳米复合粒子, (Fe₃O₄@SiO₂@polymer). 纳米复合粒子内核是磁性Fe₃O₄纳米粒子, SiO₂包裹在Fe₃O₄上能够使其稳定分散和保护其不被腐蚀氧化; 中间层是生物相容的聚天冬氨酸(PAsp)载药层; 最外层是亲水的聚乙二醇(PEG)稳定层. 磁性纳米复合粒子各层都是生物相容的, 利用静电作用将抗癌药物阿霉素(DOX)负载在磁性纳米复合粒子中, 通过PAsp的pH响应调节了DOX的释放速率.     

Tumor Microenvironment Stimuli-Responsive Fluorescence Imaging and Synergistic Cancer Therapy by Carbon-Dot–Cu2+ Nanoassemblies

A method is developed to fabricate tumor microenvironment (TME) stimuli-responsive nanoplatform for fluorescence (FL) imaging and synergistic cancer therapy via assembling photosensitizer (chlorine e6, Ce6) modified carbon dots (CDs-Ce6) and Cu²⁺. The as-obtained nanoassemblies (named Cu/CC nanoparticles, NPs) exhibit quenched FL and photosensitization due to the aggregation of CDs-Ce6. Their FL imaging and photodynamic therapy (PDT) functions are recovered efficiently once they entering tumor sites by the stimulation of TME. Introducing of Cu²⁺ not only provides extra chemodynamic therapy (CDT) function through reaction with hydrogen peroxide (H₂O₂), but also depletes GSH in tumors by a redox reaction, thus amplifying the intracellular oxidative stress and enhancing the efficacy of reactive oxygen species (ROS) based therapy. Cu/CC NPs can act as a FL imaging guided trimodal synergistic cancer treatment agent by photothermal therapy (PTT), PDT, and thermally amplified CDT.     

General Route to Synthesize Monodisperse Oxide (Hydroxide) Nanoparticles

Mono-dispersed oxide and hydroxide nanoparticles have been synthesized through the solvothermal process in alcohol-water mixtures. The products were characterized by powder x-ray diffraction (XRD) and scanning electron microscopy (SEM). Plate-like nanoparticles are obtained for Bi₂O_2.33, Fe₂O₃, and Cd(OH)₂, and spherical nanoparticles are obtained for SnO₂. The growth mechanism for the mono-dispersed nanoparticles has been preliminarily discussed.     

CuFe2O4 nanoparticles: a magnetically recoverable and reusable catalyst for the synthesis of 5-substituted 1H-tetrazoles

An efficient and economical protocol for the synthesis of 5-substituted 1H-tetrazoles from various nitriles and sodium azide is described using magnetically recoverable and reusable CuFe₂O₄ nanoparticles. A wide variety of aryl nitriles underwent [2+3] cycloaddition under mild reaction conditions to afford tetrazoles in good to excellent yields. The catalyst was magnetically separated and reused five times without significant loss of catalytic activity.     

A novel nonenzymatic hydrogen peroxide sensor based on MnO2/graphene oxide nanocomposite

A new electrocatalyst, MnO₂/graphene oxide hybrid nanostructure was successfully synthesized for the nonenzymatic detection of H₂O₂. The morphological characterization was examined by scanning electron microscopy and transmission electron microscopy. The MnO₂/graphene oxide based electrodes showed high electrochemical activity for the detection of H₂O₂ in alkaline medium. The nonenzymatic biosensors displayed good performance along with low working potential, high sensitivity, low detection limit, and long-term stability, which could be attributed to the high surface area of graphene oxide providing for the deposition of MnO₂ nanoparticles. These results demonstrate that this new nanocomposite with the high surface area and electrocatalytic activity offers great promise for new class of nanostructured electrode for nonenzymatic biosensor and energy conversion applications.     

A Nanozyme with Photo‐Enhanced Dual Enzyme‐Like Activities for Deep Pancreatic Cancer Therapy

Nanozymes have attracted extensive interest owing to their high stability, low cost and easy preparation, especially in the field of cancer therapy. However, the relatively low catalytic activity of nanozymes in the tumor microenvironment (TME) has limited their applications. Herein, we report a novel nanozyme (PtFe@Fe₃O₄) with dual enzyme‐like activities for highly efficient tumor catalytic therapy. PtFe@Fe₃O₄ shows the intrinsic photothermal effect as well as photo‐enhanced peroxidase‐like and catalase‐like activities in the acidic TME, thereby effectively killing tumor cells and overcoming the tumor hypoxia. Importantly, a possible photo‐enhanced synergistic catalytic mechanism of PtFe@Fe₃O₄ was first disclosed. We believe that this work will advance the development of nanozymes in tumor catalytic therapy.     

Determination of Four Active Oxygen Species Such as H2O2, •OH, •O2 −, and 1O2 by Luminol and CLA-Chemiluminescence Methods and Evaluation of Antioxidative Effects of Hydroxybenzoic Acids

Abstract

Simple and rapid chemiluminescence (CL) assays for H₂O₂, ?OH, ?O₂ ^? and ¹O₂ using 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol) or 2-methyl-6-phenyl-3,7-dihydroimidazo[1,2-α]pyrazin-3-one (CLA) as CL reagents were developed. The means of the intra-assay relative standard deviations of ten replicate measurements of H₂O₂ (25-120 μM), ?OH generated from Fe(II) ion (2.5-10 μM) in the presence of 980 μM H₂O₂, ?O₂ ^? generated from hypoxanthine (HX) (7-50 μM) in the presence of 9 × 10^?3 units xanthine oxidase (XO) and ¹O₂ generated from NaOCl (3-12 mM) in the presence of 97.6 μM H₂O₂ were found to be 4.0%, 2.8%, 2.4% and 8.7%, respectively. To validate the proposed methods, the scavenging abilities of three standard antioxidative compounds, such as L-ascorbic acid, (±)-α-tocopherol and superoxide dismutase (SOD) were examined for four active oxygen species and compared with those by anelectron spin resonance (ESR) spin-trapping method. In addition, the CL methods were also applied to establish the relationships between the decrease of CL intensity and the structures as well as redox characters of syringic acid, 3-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid. From the obtained results, the scavenging effects to H₂O₂, ?OH, ?O₂ ^? and ¹O₂ of other dihydroxybenzoic acids were also evaluated.     

P2Y12 Purinergic Receptor and Brain Tumors: Implications on Glioma Microenvironment

Gliomas are the most common malignant brain tumors in adults, characterized by a high proliferation and invasion. The tumor microenvironment is rich in growth-promoting signals and immunomodulatory pathways, which increase the tumor’s aggressiveness. In response to hypoxia and glioma therapy, the amounts of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) strongly increase in the extracellular space, and the purinergic signaling is triggered by nucleotides’ interaction in P2 receptors. Several cell types are present in the tumor microenvironment and can facilitate tumor growth. In fact, tumor cells can activate platelets by the ADP-P2Y₁₂ engagement, which plays an essential role in the cancer context, protecting tumors from the immune attack and providing molecules that contribute to the growth and maintenance of a rich environment to sustain the protumor cycle. Besides platelets, the P2Y₁₂ receptor is expressed by some tumors, such as renal carcinoma, colon carcinoma, and gliomas, being related to tumor progression. In this context, this review aims to depict the glioma microenvironment, focusing on the relationship between platelets and tumor malignancy.     

Theoretical study of the triplet excited state of PtPOP and the exciplexes M-PtPOP (M = Tl, Ag) in solution and comparison with ultrafast X-ray scattering results

The [Pt₂(H₂P₂O₅)₄]⁴⁻ ions in the ground and excited states and the excited-state complexes M-[Pt₂(H₂P₂O₅)₄]³⁻ and M₂-[Pt₂(H₂P₂O₅)₄]²⁻ (M = Ag, Tl) were studied in solution with various density functional theory (DFT) functionals from Gaussian 09 and Amsterdam Density Functional (ADF) programs. Calculated results were compared with ultrafast X-ray solution scattering data. Time dependent DFT (TD-DFT) calculations with the B3PW91 functional and unrestricted open shell calculations with the mPBE functional produce good agreement with the experimental results. Compared to gas phase calculations, the surrounding solvent is found to play an important role to shorten the Pt-Pt and M-Pt (M = Ag, Tl) bond lengths, lowering the molecular orbital energies and influences the molecular orbital transitions upon excitation, which stabilizes the excited transient molecules in solution.     

Synthesis of Silica@α-Fe2O3 nanospheres by surface-initiated ATRP

We reported a new method to prepare Silica@α-Fe₂O₃ nanospheres by surface-initiated atom transfer radical polymerization (ATRP). Firstly, polymerizable surfactants-modified α-Fe₂O₃ nanoparticles were prepared in water-toluene microemulsion. Then, as-synthesized α-Fe₂O₃ nanoparticles acted as the macro-monomer of surface-initiated ATRP on silica nanospheres to make target product. Morphological characterization of the product was performed using transmission electron microscopy (TEM). Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS) and diffuse reflectance UV-vis spectroscopy were used to verify the incorporation of α-Fe₂O₃ nanoparticles on silica nanosphere.     

Hydrothermal synthesis, characterization and thermochemistry of Ca2[B2O4(OH)2]·0.5H2O

A pure calcium borate Ca₂[B₂O₄(OH)₂]·0.5H₂O has been synthesized under hydrothermal condition and characterized by XRD, FT-IR and TG as well as by chemical analysis. The molar enthalpy of solution of Ca₂[B₂O₄(OH)₂]·0.5H₂O in HC1·54.582H₂O was determined. From a combination of this result with measured enthalpies of solution of H₃BO₃ in HC1·54.561H₂O and of CaO in (HCl + H₃BO₃) solution, together with the standard molar enthalpies of formation of CaO(s), H₃BO₃(s) and H₂O(l), the standard molar enthalpy of formation of −(3172.5 ± 2.5) kJ mol⁻¹ of Ca₂[B₂O₄(OH)₂]·0.5H₂O was obtained.     

Photothermal performance of MFe2O4 nanoparticles

Photothermal therapy (PTT) has emerged as one of the promising cancer therapy approaches. As a representative photothermal agent (PTA), magnetite possesses many advantages such as biodegradability and biocompatibility. However, photothermal instability hampers its further application. Herein, we systematically synthesized three kinds of ferrite nanoparticles and detailedly investigated their photothermal effect. Compared with Fe₃O₄ and MnFe₂O₄ nanoparticles, ZnFe₂O₄ nanoparticles exhibited a superior photothermal effect. After preservation for 70 days, the photothermal effect of Fe₃O₄ and MnFe₂O₄ nanoparticles observably declined while ZnFe₂O₄ nanoparticles showed slight decrease. Furthermore, in vitro experiment, ZnFe₂O₄ nanoparticles showed little toxicity to cells and achieved outstanding effect in killing cancer cells under NIR laser irradiation. Overall, through synthesizing and studying three kinds of ferrite MFe₂O₄ nanoparticles, we obtained ferrites as PTAs and learned about their changing trend in photothermal effect, expecting it can inspire further exploration of photothermal agents.