Nanocatalytic Therapy Research Articles

Near-infrared modulated photothermal/nanozymatic dual-modal strategy for combating cancer via molybdenum selenide nanourchins

BackgroundBreast cancer, a major health concern globally, often faces challenges in the non-invasive elimination of cancer cells. This has prompted researchers to explore alternative strategies, such as photothermal therapy (PTT), which takes advantage of the location of breast cancer lesions. Additionally, the tumor microenvironment with high hydrogen peroxide (H2O2) provides a key prerequisite for treating tumors with nanozymes, especially those with peroxidase (POD)-like activity. However, the overexpression of TrxR1, which maintains redox homeostasis in tumor cells, limits reactive oxygen species (ROS)-based cytotoxic therapy. This study aims to present molybdenum selenide nano urchins (MoSe2 NUs) with excellent photothermal conversion efficiency, POD-like activity and selective inhibition of TrxR1 to achieve photothermal enhanced nanocatalytic therapy for combating breast cancer.MethodsThe characterization of MoSe2 NUs synthesized by the hydrothermal method was identified by TEM, XRD, Zeta potential and DLS. Whether MoSe2 NUs in conjunction with NIR possessed POD-like activities or not was identified via a TMB colorimetric method. The photothermal characteristics of MoSe2 NUs excited by near-infrared were recorded by an infrared thermal imaging camera. The antitumor effect of MoSe2 NUs was detected by cell death staining, apoptosis assay and animal experiments. TrxR1 and apoptosis-related protein expression were identified by Western blot and Immunohistochemistry.ResultsMoSe2 NUs possessed excellent photothermal conversion efficiency, peroxidase (POD)-like activity, and selective inhibition of TrxR1. Furthermore, the photothermal effect of MoSe2 NUs can enhance their POD-like activity, allowing for accurate cancer treatment under near-infrared (NIR) light. MoSe2 NUs plus NIR and MoSe2 NUs alone exhibited in vivo tumor inhibition rates of 69.7% and 35.1%, respectively. Mechanistically, NIR-regulated MoSe2 NUs induced potent apoptosis of cancer cells by downregulating the TrxR1 and elevating intracellular ROS, thereby leading to caspase-3 cleavage.ConclusionsThis study demonstrated that MoSe2 NUs under NIR irradiation can precisely and efficiently treat breast cancer and have great potential for clinical application.Graphical

Augment of Ferroptosis with Photothermal Enhanced Fenton Reaction and Glutathione Inhibition for Tumor Synergistic Nano-Catalytic Therapy

Augment of Ferroptosis with Photothermal Enhanced Fenton Reaction and Glutathione Inhibition for Tumor Synergistic Nano-Catalytic Therapy

Pitaya-Inspired Metal-Organic Framework Nanozyme for Multimodal Imaging-Guided Synergistic Cuproptosis, Nanocatalytic Therapy, and Photothermal Therapy.

Nature often provides invaluable insights into technological innovation and the construction of nanomaterials. Inspired by the pitaya fruit's strategy of wrapping seeds within its pulp to enhance seed survival, a unique nanocomposite based on metal-organic framework (MOF)-encapsulated CuS nanoparticles (NPs) is developed. This design effectively addresses the challenge of short retention time afforded by CuS NPs for therapeutic and imaging purposes. The MOF acts as the "pitaya pulp" protecting the internal CuS NPs ("pitaya seeds"), thereby increasing their retention time in vivo. This system exhibits triple-enzyme-mimicking activities and is proposed for application in photoacoustic and magnetic resonance imaging-guided therapies, including chemodynamic therapy, photothermal therapy, and cuproptosis-related therapy. The exceptional enzyme-mimicking activities of superoxide dismutase, catalase, and peroxidase not only produce oxygen to alleviate hypoxia but also generate a reactive oxygen species (ROS) storm for effective tumor destruction. By combining these multienzymatic properties, superior photothermal performance, and Cu-induced cuproptosis, nanozyme-treated mice exhibited an 84% inhibition of tumor growth-approximately double the effect observed in mice treated with CuS NPs alone. This study presents a smart strategy for integrating imaging with therapeutic modalities, achieving exceptional outcomes for precise imaging-guided tumor therapy.

Evoking immune system to potentiate nanocatalytic therapy through activation of cGAS-STING pathway

Evoking immune system to potentiate nanocatalytic therapy through activation of cGAS-STING pathway

Cerium Vanadate Nanozyme with pH-Dependent Dual Enzymatic Activity for Glioblastoma Targeted Therapy and Postradiotherapy Damage Protection.

Nanocatalytic therapy is an emerging technology that uses synthetic nanoscale enzyme mimics for biomedical treatment. However, in the field of neuroscience, achieving neurological protection while simultaneously killing tumor cells is a technical challenge. Herein, we synthesized a biomimic and translational cerium vanadate (CeVO4) nanozyme for glioblastoma (GBM) therapy and the repair of brain damage after GBM ionizing radiation (IR). This system exhibited pH dependence: it showed potent Superoxide dismutase (SOD) enzyme activity in a neutral environment and Peroxidase (POD) enzyme activity in an acidic environment. In GBM cells, this system acted in lysosomes, causing cellular damage and reactive oxygen species (ROS) accumulation; in neuronal cells, this nanozyme could undergo lysosomal escape and nanozyme aggregation with mitochondria, reversing the mitochondrial damage caused by IR and restoring the expression level of the antiapoptotic BCL-2 protein. Mechanistically, we believe that this distribution difference is related to the specific uptake internalization mechanism and lysosomal repair pathway in neurons, and ultimately led to the dual effect of tumor killing and nerve repair in the in vivo model. In summary, this study provides insight into the repair of brain damage after GBM radiation therapy.

A multifunctional nanoplatform for chemotherapy and nanocatalytic synergistic cancer therapy achieved by amplified lipid peroxidation

Traditional cancer chemotherapy suffers from low efficacy and severe side effects, limiting its use as a first-line treatment. To address this issue, we investigated a novel way to induce lipid peroxidation (LPO), which plays an essential role in ferroptosis and may be useful against cancer cells and tumors. In this study, a pH-responsive synergistic cancer therapy nanoplatform was prepared using CaCO3 co-loaded with oleanolic acid (OA) and lipoxygenase (LOX), resulting in the formation OLCaP NP. This nanoplatform exhibited good drug release properties in an acidic tumor environment owing to the presence of CaCO3. As a result of acidic stimulation at tumor sites, the OLCaP NP released OA and LOX. OA, a chemotherapeutic drug with anticancer activity, is already known to promote the apoptosis of cancer cells, and LOX is a natural enzyme that catalyzes the oxidation of polyunsaturated fatty acids, leading to the accumulation of lipid peroxides and promoting the apoptosis of cancer cells. More importantly, OA upregulated the expression of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), which promoted enzyme-mediated LPO. Based on our combined chemotherapy and nanocatalytic therapy, the OLCaP NP not only had remarkable antitumor ability but also upregulated ACSL4 expression, allowing further amplification of LPO to inhibit tumor growth. These findings demonstrate the potential of this nanoplatform to enhance the therapeutic efficacy against tumors by inducing oxidative stress and disrupting lipid metabolism, highlighting its clinical potential for improved cancer treatment. Statement of significanceThis study presents a novel nanoplatform that combines oleanolic acid (OA), a chemotherapeutic drug, and lipoxygenase (LOX), which oxidizes polyunsaturated fatty acids to trigger apoptosis, for targeted cancer therapy. Unlike traditional treatments, our nanoplatform exhibits pH-responsive drug release, specifically in acidic tumor environments. This innovation enhances the therapeutic effects of OA and LOX, upregulating acyl-CoA synthetase long-chain family member 4 expression and amplifying lipid peroxidation to promote tumor cell apoptosis. Our findings significantly advance the existing literature by demonstrating a synergistic approach that combines chemotherapy and nanocatalytic therapy. The scientific impact of this work lies in its potential to improve cancer treatment efficacy and specificity, offering a promising strategy for clinical applications and future research in cancer therapy.

Bioorthogonal Cu Single-Atom Nanozyme for Synergistic Nanocatalytic Therapy, Photothermal Therapy, Cuproptosis and Immunotherapy.

Single-atom nanozymes (SAzymes) with atomically dispersed active sites are potential substitutes for natural enzymes. A systematic study of its multiple functions can in-depth understand SAzymes's nature, which remains elusive. Here, we develop a novel ultrafast synthesis of sputtered SAzymes by in situ bombarding-embedding technique. Using this method, sputtered copper (Cu) SAzymes (CuSA) is developed with unreported unique planar Cu-C3 coordinated configuration. To enhance the tumor-specific targeting, we employ a bioorthogonal approach to engineer CuSA, denoted as CuSACO. CuSACO not only exhibits minimal off-target toxicity but also possesses exceptional ultrahigh catalase-, oxidase-, peroxidase-like multienzyme activities, resulting in reactive oxygen species (ROS) storm generation for effective tumor destruction. Surprisingly, CuSACO can release Cu ions in the presence of glutathione (GSH) to induce cuproptosis, enhancing the tumor treatment efficacy. Notably, CuSACO's remarkable photothermal properties enables precise photothermal therapy (PTT) on tumors. This, combined with nanozyme catalytic activities, cuproptosis and immunotherapy, efficiently inhibiting the growth of orthotopic breast tumors and gliomas, and lung metastasis. Our research highlights the potential of CuSACO as an innovative strategy to utilize multiple mechanism to enhance tumor therapeutic efficacy, broadening the exploration and development of enzyme-like behavior and physiological mechanism of action of SAzymes.

Bioorthogonal Cu Single‐Atom Nanozyme for Synergistic Nanocatalytic Therapy, Photothermal Therapy, Cuproptosis and Immunotherapy

AbstractSingle‐atom nanozymes (SAzymes) with atomically dispersed active sites are potential substitutes for natural enzymes. A systematic study of its multiple functions can in‐depth understand SAzymes's nature, which remains elusive. Here, we develop a novel ultrafast synthesis of sputtered SAzymes by in situ bombarding‐embedding technique. Using this method, sputtered copper (Cu) SAzymes (CuSA) is developed with unreported unique planar Cu‐C3 coordinated configuration. To enhance the tumor‐specific targeting, we employ a bioorthogonal approach to engineer CuSA, denoted as CuSACO. CuSACO not only exhibits minimal off‐target toxicity but also possesses exceptional ultrahigh catalase‐, oxidase‐, peroxidase‐like multienzyme activities, resulting in reactive oxygen species (ROS) storm generation for effective tumor destruction. Surprisingly, CuSACO can release Cu ions in the presence of glutathione (GSH) to induce cuproptosis, enhancing the tumor treatment efficacy. Notably, CuSACO′s remarkable photothermal properties enables precise photothermal therapy (PTT) on tumors. This, combined with nanozyme catalytic activities, cuproptosis and immunotherapy, efficiently inhibiting the growth of orthotopic breast tumors and gliomas, and lung metastasis. Our research highlights the potential of CuSACO as an innovative strategy to utilize multiple mechanism to enhance tumor therapeutic efficacy, broadening the exploration and development of enzyme‐like behavior and physiological mechanism of action of SAzymes.

A Copper/Ferrous‐Engineering Redox Homeostasis Disruptor for Cuproptosis/Ferroptosis Co‐Activated Nanocatalytic Therapy in Liver Cancer

AbstractCuproptosis and ferroptosis hold great promise for overcoming apoptotic resistance in liver cancer based on their unique metal‐driven cell death modalities. However, insufficient intracellular copper and iron concentration, complicated tumor microenvironment (TME), and unclear cross‐regulatory mechanisms between cuproptosis and ferroptosis, severely restrict the therapeutic performance. Herein, copper‐doped hollow Prussian blue (CHP) nanozymes are rationally designed for loading photosensitizer indocyanine green (ICG) and O2‐saturated perfluorohexane (PFH), denoted as O2‐PFH@CHPI nanoparticles, to induce cuproptosis and ferroptosis. In response to the specific TME, the CHP nanozymes can synergistically catalyze Fenton reactions and consume endogenous glutathione, leading to the accumulation of reactive oxygen species. Upon near‐infrared irradiation, the O2‐PFH@CHPI‐enabled photothermal effect can simultaneously accelerate catalytic reactions and trigger O2 release for photodynamic therapy to promote oxidative stress. Notably, cuproptosis can be effectively activated through Cu+‐mediated dihydrolipoamide S‐acetyltransferase aggregation and Fe–S cluster protein loss. Concurrently, the tilt of redox balance is favorable for lipid peroxidation and glutathione peroxidase 4 inactivation, resulting in an augmented ferroptosis effect. Mechanistically, oxidative stress‐boosted cuproptosis and ferroptosis jointly disrupt mitochondrial metabolism, which in turn exacerbates intracellular oxidative stress, thus realizing a mutually enhanced therapeutic effect. This work may provide new guidance for utilizing copper/ferrous‐engineering nanozymes for cuproptosis/ferroptosis synergetic therapy.

A Single-Atom Manganese Nanozyme Mn-N/C Promotes Anti-Tumor Immune Response via Eliciting Type I Interferon Signaling.

Tumor microenvironment (TME)-induced nanocatalytic therapy is a promising strategy for cancer treatment, but the low catalytic efficiency limits its therapeutic efficacy. Single-atom catalysts (SACs) are a new type of nanozyme with incredible catalytic efficiency. Here, a single-atom manganese (Mn)-N/C nanozyme is constructed. Mn-N/C catalyzes the conversion of cellular H2O2 to ∙OH through a Fenton-like reaction and enables the sufficient generation of reactive oxygen species (ROS), which induces immunogenic cell death (ICD) of tumor cells and significantly promotes CD8+T anti-tumor immunity. Moreover, RNA sequencing analysis reveals that Mn-N/C treatment activates type I interferon (IFN) signaling, which is critical for Mn-N/C-mediated anti-tumor immune response. Mechanistically, the release of cytosolic DNA and Mn2+ triggered by Mn-N/C collectively activates the cGAS-STING pathway, subsequently stimulating type I IFN induction. A highly efficient single-atom nanozyme, Mn-N/C, which enhances anti-tumor immune response and exhibits synergistic therapeutic effects when combined with the anti-PD-L1 blockade, is proposed.

Biodegradable CoSnO3 nanozymes modulate pH-responsive graphene quantum dot release for synergistic chemo-sonodynamic-nanocatalytic cancer therapy

Albeit nanozymes are widely applied for nanocatalytic therapy (NCT), the unsatisfactory catalytic activity of nanozymes accompanied by complex tumor microenvironment (TME) greatly pose a barrier to the therapeutic effect of NCT. Moreover, developing a high-efficiency nanozyme with biodegradability is still a huge challenge, which hinders their further clinical translation. Herein, pH-responsive biodegradable CoSnO3 nanocubes are synthesized and employed as sonosensitizers and nanozymes due to their narrow bandgaps (1.6 eV) and Co2+/Sn4+-mediated multi-enzyme activities. After depositing the graphene quantum dot (GQD) topoisomerase inhibitors on CoSnO3 nanocubes, the heterojunction-fabricated GQD/CoSnO3 shows cascaded amplification of ROS generation, which is ascribed to the inhibition of electron-hole pair recombination, Co2+-mediated peroxidase (POD)-mimic catalytic reaction to generate OH, Co3+/Sn4+-mediated depletion of overexpressed GSH, and catalytic decomposition of endogenous H2O2 for providing more O2 for enhanced SDT. More importantly, GQD/CoSnO3 heterojunctions are slowly degraded in the weakly acidic TME, resulting the tumor-specific release of GQDs after completion of SDT, which could induce DNA damage and cell apoptosis for chemotherapy to further enhanced the antitumor efficacy. The synergetic therapeutic efficacy of GQD/CoSnO3 heterojunctions through chemotherapy, SDT, and NCT could realize “three-in-one” multimodal oncotherapy to completely eliminate tumors without recurrence. This work provides a paradigm of exploring pH-responsive biodegradable nanozymes as a drug carrier to realize tumor-specific drug release for enhanced SDT and NCT.

Metabolism-Regulating Nanozyme System for Advanced Nanocatalytic Cancer Therapy.

Nanocatalytic therapy, an emerging approach in cancer treatment, utilizes nanomaterials to initiate enzyme-mimetic catalytic reactions within tumors, inducing tumor-suppressive effects. However, the targeted and selective catalysis within tumor cells is challenging yet critical for minimizing the adverse effects. The distinctive reliance of tumor cells on glycolysis generates abundant lactate, influencing the tumor's pH, which can be manipulated to selectively activate nanozymatic catalysis. Herein, small interfering ribonucleic acid (siRNA) targeting lactate transporter-mediated efflux is encapsulated within the iron-based metal-organic framework (FeMOF) and specifically delivered to tumor cells through cell membrane coating. This approach traps lactate within the cell, swiftly acidifying the tumor cytoplasm and creating an environment for boosting the catalysis of the FeMOF nanozyme. The nanozyme generates hydroxyl radical (·OH) in the reversed acidic environment, using endogenous hydrogen peroxide (H2O2) produced by mitochondria as a substrate. The induced cytoplasmic acidification disrupts calcium homeostasis, leading to mitochondrial calcium overload, resulting in mitochondrial dysfunction and subsequent tumor cell death. Additionally, the tumor microenvironment is also remodeled, inhibiting migration and invasion, thus preventing metastasis. This groundbreaking strategy combines metabolic regulation with nanozyme catalysis in a toxic drug-free approach for tumor treatment, holding promise for future clinical applications.

Mild-photothermal and nanocatalytic therapy for obesity and associated diseases.

Background: Current anti-obesity medications suffer from limited efficacy and side-effects because they act indirectly on either the central nervous system or gastrointestinal system. Herein, this work aims to introduce a transdermal photothermal and nanocatalytic therapy enabled by Prussian blue nanoparticles, which directly act on obese subcutaneous white adipose tissue (sWAT) to induce its beneficial remodeling including stimulation of browning, lipolysis, secretion of adiponectin, as well as reduction of oxidative stress, hypoxia, and inflammation. Methods: Prussian blue nanoparticles were synthesized and incorporated into silk fibroin hydrogel for sustained retention. The efficacy of mild photothermal (808 nm, 0.4 W/cm2, 5 min) and nanocatalytic therapy (mPTT-NCT) was assessed both in vitro (3T3-L1 adipocytes) and in vivo (obese mice). The underlying signaling pathways are carefully revealed. Additionally, biosafety studies were conducted to further validate the potential of this therapy for practical application. Results: On 3T3-L1 adipocytes, mPTT-NCT was able to induce browning, enhance lipolysis, and alleviate oxidative stress. On obese mice model, the synergistic treatment led to not only large mass reduction of the targeted sWAT (53.95%) but also significant improvement of whole-body metabolism as evidenced by the substantial decrease of visceral fat (65.37%), body weight (9.78%), hyperlipidemia, and systemic inflammation, as well as total relief of type 2 diabetes. Conclusions: By directly targeting obese sWAT to induce its beneficial remodeling, this synergistic therapy leads to significant improvements in whole-body metabolism and the alleviation of obesity-related conditions, including type 2 diabetes. The elucidation of underlying signaling pathways provides fundamental insights and shall inspire new strategies to combat obesity and its associated diseases.

Bimetallic doped carbon dot nanozymes for enhanced sonodynamic and nanocatalytic therapy

The conventional inorganic semiconductors are not suitable for acting as nanozymes or sonosensitizers for in vivo therapeutic nanomedicine owing to the lack of excellent biocompatibility. Biocompatible carbon dots (CDs) exhibit...

V-doped MoS2 nanozymes providing reactive oxygen species and depleting glutathione for photothermally-enhanced nanocatalytic therapy.

Introduction: The tumor microenvironment and multidrug resistance of tumor cells seriously impair the activity of the nanozymes. Methods: Herein, a polyethylene glycol (PEG)-modified vanadium-doped molybdenum disulfide (V-MoS2@PEG) nanozymes were constructed to enhance anti-tumor activity through multi-enzymatic catalysis and photothermal effect with simultaneous reactive oxygen species replenishment and glutathione depletion. Results and discussion: V-MoS2@PEG nanosheets exerted peroxidase activity by causing molybdenum ion (Mo4+) to react with hydrogen peroxide to form toxic hydroxyl radicals (·OH). Meanwhile, the V-doping can deplete glutathione avoiding ·OH consumption. In addition, the high heat generated by V-MoS2@PEG nanozymes under near-infrared laser irradiation brought about a desirable local temperature gradient, which produced an enhanced catalytic effect by promoting band bending. Furthermore, the photothermally inspired polarized charge increased the permeability of the tumor cell membrane and promoted further aggregation of the nanozymes, which realized the combination of photothermal therapy with multi-enzymatic catalysis, solved the problem of multi-enzyme catalysis, and improved the anti-tumor efficiency.

Precise design of dual active-site catalysts for synergistic catalytic therapy of tumors.

A proven and promising method to improve the catalytic performance of single-atom catalysts through the interaction between bimetallic atoms to change the active surface sites or adjust the catalytic sites of reactants is reported. In this work, we used an iron-platinum bimetallic reagent as the metal source to precisely synthesise covalent organic framework-derived diatomic catalysts (FePt-DAC/NC). Benefiting from the coordination between the two metal atoms, the presence of Pt single atoms can successfully regulate Fe-N3 activity. FePt-DAC/NC exhibited a stronger ability to catalyze H2O2 to produce toxic hydroxyl radicals than Fe single-atom catalysts (Fe-SA/NC) to achieve chemodynamic therapy of tumors (the catalytic efficiency improved by 186.4%). At the same time, under the irradiation of an 808 nm laser, FePt-DAC/NC exhibited efficient photothermal conversion efficiency to achieve photothermal therapy of tumors. Both in vitro and in vivo results indicate that FePt-DAC/NC can efficiently suppress tumor cell growth by a synergistic therapeutic effect with photothermally augmented nanocatalytic therapy. This novel bimetallic dual active-site monodisperse catalyst provides an important example for the application of single-atom catalysts in the biomedical field, highlighting its promising clinical potential.

Cobalt-based hybrid nanoparticles loaded with curcumin for ligand-enhanced synergistic nanocatalytic therapy/chemotherapy combined with calcium overload.

The therapeutic efficacy of Fenton or Fenton-like nanocatalysts is usually restricted by the inappropriate pH value and limited concentration of hydrogen peroxide (H2O2) at the tumor site. Herein, calcium carbonate (CaCO3)-mineralized cobalt silicate hydroxide hollow nanocatalysts (CSO@CaCO3, CC) were synthesized and loaded with curcumin (CCC). This hybrid system can simultaneously realize nanocatalytic therapy, chemotherapy and calcium overload. With the stabilization of liposomes, CCC is able to reach the tumor site smoothly. The CaCO3 shell first degrades in an acidic tumor environment, releasing Cur and Ca2+, and the pH value of the tumor is increased simultaneously. Then the exposed CSO catalyzes the Fenton-like reaction to convert H2O2 into ˙OH and enhances the cytotoxicity of curcumin (Cur) by catalytically oxidizing it to a ˙Cur radical. Curcumin not only induces the chemotherapy effect but also serves as a nucleophilic ligand and an electron donor in the catalytic system, enhancing the Fenton-like activity of CCC by electron transfer. In addition, calcium overload also amplifies the efficacy of ROS-based therapy. In vitro and in vivo results show that CCC exhibited an excellent synergistic tumor inhibition effect without any clear side effect. This work proposes a novel concept of nanocatalytic therapy/chemotherapy synergistic mechanism by the ligand-induced enhancement of Fenton-like catalytic activity, and inspires the construction of combined therapeutic nanoplatforms and multifunctional nanocarriers for drug and ion delivery in the future.

Unraveling Ros Conversion Through Enhanced Enzyme-Like Activity with Copper-Doped Cerium Oxide for Tumor Nanocatalytic Therapy.

Nanozyme catalytic therapy for cancer treatments has become one of the heated topics, and the therapeutic efficacy is highly correlated with their catalytic efficiency. In this work, three copper-doped CeO2 supports with various structures as well as crystal facets are developed to realize dual enzyme-mimic catalytic activities, that is superoxide dismutase (SOD) to reduce superoxide radicals to H2 O2 and peroxidase (POD) to transform H2 O2 to ∙OH. The wire-shaped CeO2 /Cu-W has the richest surface oxygen vacancies, and a low level of oxygen vacancy (Vo) formation energy, which allows for the elimination of intracellular reactive oxygen spieces (ROS) and continuous transformation to ∙OH with cascade reaction. Moreover, the wire-shaped CeO2 /Cu-W displays the highest toxic ∙OH production capacity in an acidic intracellular environment, inducing breast cancer cell death and pro-apoptotic autophagy. Therefore, wire-shaped CeO2 /Cu nanoparticles as an artificial enzyme system can have great potential in the intervention of intracellular ROS in cancer cells, achieving efficacious nanocatalytic therapy.

Boosting Reactive Oxygen Species Generation with a Dual-Catalytic Nanomedicine for Enhanced Tumor Nanocatalytic Therapy.

Generating lethal reactive oxygen species (ROS) within tumors by nanocatalytic medicines is an advanced strategy for tumor-specific therapy in recent years. Nevertheless, the low yield of ROS restrains its therapeutic efficiency. Herein, a dual-catalytic nanomedicine based on tumor microenvironment (TME)-responsive liposomal nanosystem co-delivering CuO2 and dihydroartemisinin (DHA) (LIPSe@CuO2&DHA) is developed to boost ROS generation against tumor. The liposomal nanosystem can degrade in the ROS-overexpressed TME and liberate CuO2 and DHA to initiate Cu-based dual-catalytic ROS generation. Serving as generators of H2O2 and Cu2+, CuO2 can self-produce plenty of toxic hydroxyl radicals via Fenton-like reaction in the acidic TME. Meanwhile, the released Cu2+ can catalyze DHA to generate cytotoxic C-centered radicals. Together, the self-supplied H2O2 and Cu-based dual-catalytic reaction greatly increase the intratumoral level of lethal ROS. Importantly, Cu2+ can decrease the GSH-mediated scavenging effect on the produced ROS via a redox reaction and undergo a Cu2+-to-Cu+ conversion to enhance the Fenton-like reaction, further guaranteeing the high efficiency of ROS generation. Resultantly, LIPSe@CuO2&DHA induces remarkable cancer cell death and tumor growth inhibition, which may present a promising nanocatalytic medicine for cancer therapy.

PdMo nanoflowers for endogenous/exogenous-stimulated nanocatalytic therapy.

The clinical application of reactive oxygen species (ROS)-mediated tumor treatment has been critically limited by inefficient ROS generation. Herein, we rationally synthesized and constructed the three-dimensional PdMo nanoflowers through a one-pot solvothermal reduction method for elaborately regulated peroxidase-like enzymatic activity and glutathione peroxidase-like enzymatic activity, to promote oxidation ROS evolvement and antioxidation glutathione depletion for achieving intensive ROS-mediated tumor therapy. The three-dimensional superstructure composed of two-dimensional nanosheet subunits can solve the issues by avoiding the appearance of tightly stacked crystalline nanostructures. Significantly, Mo is chosen as a second metal to alloy with Pd because of its more chemical valence and negative ionization energy than Pd for improved electron transfer efficiencies and enhanced enzyme-like activities. In addition, the photothermal effect generated by PdMo nanoflowers could also enhance its enzymatic activities. Thus, this work provides a promising paradigm for achieving highly ROS-mediated tumor therapeutic efficacy by regulating the multi-enzymatic activities of Pd-based nanoalloys.