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1.
The unique tumor microenvironment (TME) facilitates cancer proliferation and metastasis, and it is hard to cure cancer completely via monotherapy. Herein, a multifunctional cascade bioreactor based on hollow mesoporous Cu2MoS4 (CMS) loaded with glucose oxidase (GOx) is constructed for synergetic cancer therapy by chemo‐dynamic therapy (CDT)/starvation therapy/phototherapy/immunotherapy. The CMS harboring multivalent elements (Cu1+/2+, Mo4+/6+) exhibit Fenton‐like, glutathione (GSH) peroxidase‐like and catalase‐like activity. Once internalized into the tumor, CMS could generate ·OH for CDT via Fenton‐like reaction and deplete overexpressed GSH in TME to alleviate antioxidant capability of the tumors. Moreover, under hypoxia TME, the catalase‐like CMS could react with endogenous H2O2 to generate O2 for activating the catalyzed oxidation of glucose by GOx for starvation therapy accompanied with the regeneration of H2O2. The regenerated H2O2 can devote to Fenton‐like reaction for realizing GOx‐catalysis‐enhanced CDT. Meanwhile, the CMS under 1064 nm laser irradiation shows remarkable tumor‐killing ability by phototherapy due to its excellent photothermal conversion efficiency (η = 63.3%) and cytotoxic superoxide anion (·O2?) generation performance. More importantly, the PEGylated CMS@GOx‐based synergistic therapy combined with checkpoint blockade therapy could elicit robust immune responses for both effectively ablating primary tumors and inhibiting cancer metastasis.  相似文献   

2.
Osteosarcoma (OS) is the most serious bone malignancy, and the survival rate has not significantly improved in the past 40 years. Thus, it is urgent to develop a new strategy for OS treatment. Chemodynamic therapy (CDT) as a novel therapeutic method can destroy cancer cells by converting endogenous hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (·OH). However, the therapeutic efficacy of CDT is severely limited by the low catalytic efficiency and overexpressed glutathione (GSH). Herein, an excellent nanocatalytic platform is constructed via a simple solvothermal method using F127 as a soft template to form the hollow copper ferrite (HCF) nanoparticle, followed by the coating of polydopamine on the surface and the loading of doxorubicin (DOX). The Fe3+ and Cu2+ released from HCF@polydopamine (HCFP) can deplete GSH through the redox reactions, and then trigger the H2O2 to generate ·OH by Fenton/Fenton-like reaction, resulting in enhanced CDT efficacy. Impressively, the photothermal effect of HCFP can further enhance the efficiency of CDT and accelerate the release of DOX. Both in vitro and in vivo experiments reveal that the synergistic chemodynamic/photothermal/chemo-therapy exhibits a significantly enhanced anti-OS effect. This work provides a promising strategy for OS treatment.  相似文献   

3.
The conventional approach in cancer nanomedicine involves advanced drug nanocarriers delivering preloaded therapeutics to targeted tumor sites to maximize drug efficiency. However, both cancer drugs and nanocarriers inevitably produce side effects and systemic toxicity. Herein, hemoglobin nanocrystals (HbC) as drug-free theranostic nanoformulations with the tumor microenvironment (TME) activated diagnostic and therapeutic abilities towards colon tumors are introduced. HbC can release Fe2+ oxidized to Fe3+ in the Fenton reaction with tumor endogenous H2O2, concurrently with the generation of cytotoxic hydroxyl radicals (•OH) that allow for chemodynamic therapy (CDT). Furthermore, in situ-produced Fe3+ reacts with colon tumor-abundant H2S, resulting in the production of Fe1−xS, which provides magnetic resonance imaging (MRI) contrast and allows for NIR light-inducible photothermal therapy (PTT). In vitro and in vivo studies revealed that HbC produced CDT towards 4T1 tumors, and MRI-guided, synergistically enhanced combination of CDT and PTT against H2S abundant colon tumors (CT26), with negligible toxicity towards normal tissues, enlightening HbC as highly efficient and biocompatible TME activated theranostic nanoplatform specific against colon cancer without any traditional drugs and drug carriers.  相似文献   

4.
Chemodynamic therapy (CDT) relies on the tumor microenvironment (e.g., high H2O2 level) responsive Fenton-like reactions to produce hydroxyl radicals (·OH) against tumors. However, endogenous H2O2 is insufficient for effective chemodynamic responses. An NAD(P)H: quinone oxidoreductase 1 (NQO1)high catalase (CAT)low therapeutic window for the use of NQO1 bioactive drug β-lapachone (β-Lap) is first identified in endometrial cancer (EC). Accompanied by NADH depletion, NQO1 catalyzes β-Lap to produce excess H2O2 and initiate oxidative stress, which selectively suppress NQO1high EC cell proliferation, induce DNA double-strand breaks, and promote apoptosis. Moreover, shRNA-mediated NQO1 knockdown or dicoumarol rescues NQO1high EC cells from β-Lap-induced cytotoxicity. Arginine-glycine-aspartic acid (RGD)-functionalized iron-based metal-organic frameworks (MOF(Fe)) further promote the conversion of the accumulated H2O2 into highly oxidative ·OH, which in turn, exacerbates the oxidative damage to RGD-positive target cells. Furthermore, mitophagy inhibition by Mdivi-1 blocks a powerful antioxidant defense approach, ultimately ensuring the anti-tumor efficacy of stepwise-amplified reactive oxygen species signals. The tumor growth inhibition rate (TGI) is about 85.92%. However, the TGI of MOF(Fe)-based synergistic antitumor therapy decreases to only 50.46% in NQO1-deficient KLE tumors. Tumor-specific chemotherapy and CDT-triggered therapeutic modality present unprecedented therapeutic benefits in treating NQO1high EC.  相似文献   

5.
Chemodynamic therapy (CDT) has attracted considerable attention recently, but the poor reaction kinetics restrict its practical utility in clinic. Herein, glucose oxidase (GOx) functionalized ancient pigment nanosheets (SrCuSi4O10, SC) for programmable near‐infrared II (NIR‐II) photothermal‐enhanced starvation primed CDT is developed. The SC nanosheets (SC NSs) are readily exfoliated from SC bulk suspension in water and subsequently functionalized with GOx to form the nanocatalyst (denoted as SC@G NSs). Upon laser irradiation, the photothermal effect of SC NSs can enhance the catalytic activity of GOx for NIR‐II photothermal‐enhanced starvation therapy, which effectively eliminates intratumoral glucose and produces abundant hydrogen peroxide (H2O2). Importantly, the high photothermal‐conversion efficiency (46.3%) of SC@G NSs in second biological window permits photothermal therapy of deep‐seated tumors under the guidance of NIR‐II photoacoustic imaging. Moreover, the acidity amplification due to gluconic acid generation will in turn accelerate the degradation of SC NSs, facilitating the release of strontium (Sr) and copper (Cu) ions. Both the elevated H2O2 and the released ions will prime the Cu2+/Sr2+‐H2O2 reaction for enhanced CDT. Thus, a programmable NIR‐II photothermal‐enhanced starvation primed CDT is established to combat cancer with minimal side effects.  相似文献   

6.
Nowadays, Fenton chemistry-based chemodynamic therapy (CDT) is an emerging approach to killing tumor cells by converting endogenous H2O2 into cytotoxic hydroxyl radicals (·OH). However, the elimination of ·OH by intracellular overexpressed glutathione (GSH) results in unsatisfactory antitumor efficiency. In addition, the single mode of consuming GSH and undesirable drug loading efficiency cannot guarantee the efficient cancer cells killing effect. Herein, a simple one-step strategy for the construction of Fe3+-naphthazarin metal–phenolic networks (FNP MPNs) with ultrahigh loading capacity, followed by the modification of NH2-PEG-NH2, is developed. The carrier-free FNP MPNs can be triggered by acid and GSH, and rapidly release naphthazarin and Fe3+, which is further reduced to Fe2+ that exerts Fenton catalytic activity to produce abundant ·OH. Meanwhile, the Michael addition between naphthazarin and GSH can lead to GSH depletion and thus achieve tumor microenvironment (TME)-triggered enhanced CDT, followed by activating ferroptosis and apoptosis. In addition, the reduced Fe2+ as a T1-weighted contrast agent endows the FNP MPNs with magnetic resonance imaging (MRI) functionality. Overall, this work is the debut of naphthazarin as ligands to fabricate functional MPNs for effectively depleting GSH, disrupting intracellular redox homeostasis, and enhancing CDT effects, which opens new perspectives on multifunctional MPNs for tumor synergistic therapy.  相似文献   

7.
A magnetic Cu/CuFe2O4 nanocomposite was synthesized by a facile one-pot solvothermal method and characterized as an excellent Fenton-like catalyst for methylene blue (MB) degradation. The content of zero-valent copper (Cu0) in Cu/CuFe2O4 composite could be simply controlled by changing the dosage of sodium acetate in the synthetic process, and the Fenton-like catalytic performance of Cu/CuFe2O4 composite enhanced with increasing the Cu0 content. In the presence of H2O2 (15 mM), the as-synthesized 3-Cu/CuFe2O4 nanocomposite could remove 99% of MB (50 mg/L) after only 4 min at pH 2.50, greatly higher than that of pure CuFe2O4 and Cu0 under the same condition. The enhancement activity of Cu/CuFe2O4 nanocomposite was due to the synergistic effect between Cu0 and CuFe2O4. The radical capture experiments and coumarin fluorescent probe technique confirmed that MB was degraded mainly by the attack of OH· radicals in Cu/CuFe2O4–H2O2 system.  相似文献   

8.
Rational design of tumor microenvironment (TME)-activated nanocomposites provides an innovative strategy to construct responsive oncotherapy. In colorectal cancer (CRC), the specific physiological features are the overexpressed endogenous H2S and slightly acidic microenvironment. Here, a core–shell Cu2O@CaCO3 nanostructure for CRC “turn-on” therapy is reported. With CaCO3 responsive to pH decomposition and Cu2O responsive to H2S sulfuration, Cu2O@CaCO3 can be triggered “on” into the therapeutic mode by the colorectal TME. When the CaCO3 shell decomposes and releases calcium in acidic colorectal TME, the loss of protection from the CaCO3 shell exposes the Cu2O core to be sulfuretted by H2S to form metabolizable Cu31S16 nanocrystals that gain remarkably strong near-infrared absorption. After modifying hyaluronic acid, Cu2O@CaCO3 can achieve synergistic CRC-targeted and TME-triggered photothermal/photodynamic/chemodynamic/calcium-overload-mediated therapy. Moreover, it is found that the generation of hyperthermia and oxidative stress from Cu2O@CaCO3 nanocomposites can efficiently reprogram the macrophages from the M2 phenotype to the M1 phenotype and initiate a vaccine-like immune effect after primary tumor removal, which further induces an immune-favorable TME and intense immune responses for anti-CD47 antibody to simultaneously inhibit CRC distant metastasis and recurrence by immunotherapy.  相似文献   

9.
The tumor microenvironment (TME) has been increasingly recognized as a crucial contributor to tumorigenesis. Based on the unique TME for achieving tumor‐specific therapy, here a novel concept of photothermal‐enhanced sequential nanocatalytic therapy in both NIR‐I and NIR‐II biowindows is proposed, which innovatively changes the condition of nanocatalytic Fenton reaction for production of highly efficient hydroxyl radicals (?OH) and consequently suppressing the tumor growth. Evidence suggests that glucose plays a vital role in powering cancer progression. Encouraged by the oxidation of glucose to gluconic acid and H2O2 by glucose oxidase (GOD), an Fe3O4/GOD‐functionalized polypyrrole (PPy)‐based composite nanocatalyst is constructed to achieve diagnostic imaging‐guided, photothermal‐enhanced, and TME‐specific sequential nanocatalytic tumor therapy. The consumption of intratumoral glucose by GOD leads to the in situ elevation of the H2O2 level, and the integrated Fe3O4 component then catalyzes H2O2 into highly toxic ?OH to efficiently induce cancer‐cell death. Importantly, the high photothermal‐conversion efficiency (66.4% in NIR‐II biowindow) of the PPy component elevates the local tumor temperature in both NIR‐I and NIR‐II biowindows to substaintially accelerate and improve the nanocatalytic disproportionation degree of H2O2 for enhancing the nanocatalytic‐therapeutic efficacy, which successfully achieves a remarkable synergistic anticancer outcome with minimal side effects.  相似文献   

10.
Activatable theranostic agents that can be activated by tumor microenvironment possess higher specificity and sensitivity. Here, activatable nanozyme‐mediated 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) loaded ABTS@MIL‐100/poly(vinylpyrrolidine) (AMP) nanoreactors (NRs) are developed for imaging‐guided combined tumor therapy. The as‐constructed AMP NRs can be specifically activated by the tumor microenvironment through a nanozyme‐mediated “two‐step rocket‐launching‐like” process to turn on its photoacoustic imaging signal and photothermal therapy (PTT) function. In addition, simultaneously producing hydroxyl radicals in response to the high H2O2 level of the tumor microenvironment and disrupting intracellular glutathione (GSH) endows the AMP NRs with the ability of enhanced chemodynamic therapy (ECDT), thereby leading to more efficient therapeutic outcome in combination with tumor‐triggered PTT. More importantly, the H2O2‐activated and acid‐enhanced properties enable the AMP NRs to be specific to tumors, leaving the normal tissues unharmed. These remarkable features of AMP NRs may open a new avenue to explore nanozyme‐involved nanoreactors for intelligent, accurate, and noninvasive cancer theranostics.  相似文献   

11.
The repair of bone defects caused by osteosarcoma resection remains a clinical challenge because of the tumor recurrence and bacterial infection. Combining tumor and bacterial therapy with bone regeneration properties in bone implants is a promising strategy for the treatment of osteosarcoma. Here, a layer of MgO/FeOx nanosheet is constructed on the Ti implant to prevent tumor recurrence and bacterial infection, while simultaneously accelerating bone formation. This MgO/FeOx double metal oxide demonstrates good peroxidase activity to catalyze H2O2, which is rich in tumor microenvironment, to form reactive oxygen species (ROS), and shows good photothermal conversion capacity to produce photothermal effect, thus synergistically killing tumor cells and eliminating tumor tissue. In addition, it generates a local alkaline surface microenvironment to inhibit the energy metabolism of bacteria to enhance the photothermal antibacterial effect. Furthermore, benefiting from the generation of a Mg ion-containing alkaline microenvironment, this MgO/FeOx film can promote the osteogenic differentiation of osteoblast and angiogenesis of vascular endothelial cells in vitro as well as accelerated bone formation in vivo. This study proposes a multifunctional platform for integrating tumor and bacterial therapy and bone regeneration, which has good application prospects for the treatment of osteosarcoma.  相似文献   

12.
Smart theranostics agents triggered by endogenous H2S with combined activated photoacoustic imaging and photothermal therapy can improve the diagnosis and treatment of colon cancer. However, the low theranostic performance of the current smart theranostics agents after the triggering step has limited their further application. In this work, the theranostic performance of endogenous H2S‐triggered Au@Cu2O for the diagnosis and treatment of colon cancer, which is generated from the localized surface plasmon resonance coupling effect between a noble metal (Au) and a semiconductor (Cu2O), is investigated. Compared with Cu2O, the prepared H2S‐triggered Au@Cu2O shows a significantly stronger absorption at the near‐infrared region, such as a ≈2.1 times change at 808 nm, giving a photothermal conversion efficiency increase of ≈1.2 times. More importantly, Au@Cu2O still exhibits good photoacoustic imaging contrast and photothermal properties for treatment of colon cancer in vivo even at very low injection doses. This work not only investigates an endogenous H2S‐triggered Au@Cu2O theranostic agent with enhanced theranostic performance for colon cancer but also provides a novel strategy for designing high‐performance theranostic agents.  相似文献   

13.
The interaction between platelets and circulating tumor cells (CTCs) contributes to distal tumor metastasis by protecting CTCs from immunological assault and shear stress, which can be disrupted by nitric oxide (NO) through inhibiting platelet-mediated adhesion. To eradicate primitive tumors and inhibit CTC-based pulmonary metastasis, a novel biomimetic nanomedicine (mCuMNO) is designed by encapsulating Cu+-responsive S-nitrosoglutathione as a NO donor into a copper-based metal-organic framework (CuM). This work discovers that mCuMNO can target tumor regions and deplete local glutathione (GSH) to reduce Cu2+ to Cu+, followed by triggering NO release and hydroxyl radicals ( · OH) production, thereby interrupting platelet/CTC interplay and contributing to chemodynamic therapy. Detailed studies demonstrate that mCuMNO exhibits high efficiency and safety in tumor therapy and antimetastasis activity, sheding new light on the development of CuM-based tumor synthetic therapy.  相似文献   

14.
The synthesis and characterization of UiO‐type metal–organic framework nanoparticles (NMOFs) composed of Zr4+ ions bridged by 2,2′‐bipyridine‐5,5′‐dicarboxylic acid ligands and the postmodification of the NMOFs with Cu2+ ions are described. The resulting Cu2+‐modified NMOFs, Cu2+‐NMOFs, exhibit peroxidase‐like catalytic activities reflected by the catalyzed oxidation of Amplex‐Red to the fluorescent Resorufin by H2O2, the catalyzed oxidation of dopamine to aminochrome by H2O2, and the catalyzed generation of chemiluminescence in the presence of luminol/H2O2. Also, the Cu2+‐NMOFs mimic NADH peroxidase functions and catalyze the oxidation of dihydronicotinamide adenine dinucleotide, NADH, to nicotinamide adenine dinucleotide, NAD+, in the presence of H2O2. The Cu2+‐NMOFs‐catalyzed generation of chemiluminescence in the presence of luminol/H2O2 is used to develop a glucose sensor by monitoring the H2O2 formed by the aerobic oxidation of glucose to gluconic acid in the presence of glucose oxidase. Furthermore, loading the Cu2+‐NMOFs with fluorescein and activating the catalyzed generation of chemiluminescence in the presence of luminol/H2O2 yield an efficient chemiluminescence resonance energy transfer (CRET) process to the fluorescein reflected by the activation of the fluorescence of the dye (λ = 520 nm, CRET efficiency 35%).  相似文献   

15.
Cu3V2O7(OH)2·2H2O nanowires have been synthesized in high yield through a simple and facile low-temperature hydrothermal approach without any template or surfactants. XRD, TG, FE-SEM, TEM and HRTEM were used to characterize the product. The results indicated that the product consisted of wirelike crystals about 80 nm in diameter and length up to several micrometers. The formation of wirelike structure of Cu3V2O7(OH)2·2H2O depended crucially on the reaction time and pH value of the precursor suspensions. The optical absorption spectrum indicates that the Cu3V2O7(OH)2·2H2O nanowires have a direct band gap of 1.94 eV.  相似文献   

16.
Plasmonic gold nanorods (Au NRs)–copper sulfide heterostructures have recently attracted much attention owing to the synergistically enhanced photothermal properties. However, the facile synthesis and interface tailoring of Au NRs–copper sulfide heterostructures remain a formidable challenge. In this study, the rational design and synthesis of Au NRs–Cu7S4 heterostructures via a one‐pot hydrothermal process is reported. Specifically, core–shell and dumbbell‐like Au NRs–Cu7S4 heterostructures are obtained with well‐controlled interfaces by employing the Au NRs with different aspect ratios. Both core–shell and dumbbell‐like Au NRs–Cu7S4 have proven effective as photothermal therapy agents, which offer both high photothermal stability and significant photothermal conversion efficiency up to 62%. The finite‐difference time domain simulation results confirm the coupling effect that leads to the enhanced local field as well as the optical absorption at the heterostructure interface. Importantly, these Au NRs–Cu7S4 heterostructures can be compatibly used as an 808 nm laser‐driven photothermal therapy agents for the efficient photothermal therapy of cancer cells in vitro. This study will provide new insight into the design of other noble metal–semiconductor heterostructures for a broad range of applications utilizing surface plasmon resonance enhancement phenomena.  相似文献   

17.
Ion-interference therapy (IIT) utilizes ions to disturb intracellular biological processes and has been received increasing attention in tumor treatments recently. However, the low therapeutic efficiency still hinders its further biological applications. Herein, via a simple and one-pot gas diffusion process, polyethylene glycol (PEG)-modified Mn2+ ions and usnic acid (UA)-incorporated CaCO3 nanomaterials (PEGCaMnUA) as Ca2+/Mn2+ ions reservoirs are prepared for magnetic resonance imaging (MRI)-guided UA-elevated IIT. Among PEGCaMnUA, UA not only increases cytoplasmic Ca2+ ions to amplify Ca2+ overload caused by CaCO3 decomposition, but also enhances Mn2+ ions-participated Fenton-like biocatalysis by intracellular H2O2 generation and glutathione consumption. Then increasing the intracellular oxidative stress and decreasing the triphosadenine supply induce apoptosis together, resulting in UA-boosted IIT. The simple and efficient design of the dual ions reservoirs will contribute to improve the antitumor activity of IIT and further development of calcium-based nanomaterials in the future.  相似文献   

18.
The contamination of subsurface soils with petroleum hydrocarbons is a widespread environmental problem. The objective of this study was to evaluate the potential of applying waste basic oxygen furnace slag (BOF slag) as the catalyst to enhance the Fenton-like oxidation to remediate fuel oil or diesel contaminated soils. The studied controlling factors that affect the removal efficiency of petroleum hydrocarbons included concentrations of H2O2, BOF slag dosages, types of petroleum hydrocarbons (e.g., fuel oil and diesel), and types of iron mineral. Experimental results indicate that oxidation of petroleum hydrocarbon via the Fenton-like process can be enhanced with the addition of BOF slag. Results from the X-ray powder diffraction analysis reveal that the major iron type of BOF slag/sandy loam system was iron mineral (e.g., α-Fe2O3 and α-FeOOH). Approximately 76% and 96% of fuel oil and diesel removal were observed (initial total petroleum hydrocarbon (TPH) concentration = 10,000 mg kg−1), respectively, with the addition of 15% of H2O2 and 100 g kg−1 of BOF slag after 40 h of reaction. Because BOF slag contains extractable irons such as amorphous iron and soluble iron, it can act as an iron sink to supply iron continuously for Fenton-like oxidation. Results demonstrate that Fenton-like oxidation catalyzed by BOF slag is a potential method to be able to remediate petroleum-hydrocarbon contaminated soils efficiently and effectively.  相似文献   

19.
The redox homeostasis in tumors enhances their antioxidant defense ability, limiting reactive oxygen species mediated tumor therapy efficacy. The development of strategies for specific and continuous disruption of the redox homeostasis in tumor cells facilitates the improvement of the cancer therapeutic effect by promoting the apoptosis of tumor cells. Herein, a responsively biodegradable targeting multifunctional integrated nanosphere (HDMn-QDs/PEG-FA) is designed to enhance the anti-tumor efficacy by triggering intratumoral cascade reactions to effectively disrupt intracellular redox homeostasis. Once HDMn-QDs/PEG-FA enters tumor cells, manganese dioxide (MnO2) shell on the surface of nanosphere consumes glutathione (GSH) to produce Mn2+, enabling enhanced chemodynamic therapy (CDT) via a Fenton-like reaction and T1-weighted magnetic resonance imaging. Meanwhile, the degradation of MnO2 can also cause the fluorescence recovery of quantum dots conjugated on the surface of the shell, realizing “turn-on” fluorescence imaging. In addition, the doxorubicin is released because of the cleavage of the embedded S S bond in the hybrid core framework by GSH. A superior synergistic therapeutic efficiency combined CDT and chemotherapy is shown by HDMn-QDs/PEG-FA in vivo. The tumor-inhibition rate reaches to 94.8% and does not cause normal tissue damage due to the good targeting and tumor microenvironment-specific response.  相似文献   

20.
Uniform Cu3(OH)2V2O7·2H2O microspheres assembled by nanorods have been fabricated through a simple hydrothermal method for the first time employing copper hydroxide carbonate (Cu2(OH)2CO3) as copper source without the assistance of any template or surfactant. The formation mechanism was proposed based on the evolution of this morphology as a function of hydrothermal time. The Electrochemical measurements revealed that the Cu3(OH)2V2O7·2H2O microspheres displayed a high discharge capacity, which indicates that the Cu3(OH)2V2O7·2H2O microspheres are promising cathode candidates for primary lithium batteries used in long term implantable cardioverter defibrillators (ICD).  相似文献   

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