摘要 :
Nanocatalysts are promising tumor therapeutics due to their ability to induce
reactive oxygen species in the tumor microenvironment. Although increasing
metal loading can improve catalytic activity, the quandary of high metal co...
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Nanocatalysts are promising tumor therapeutics due to their ability to induce
reactive oxygen species in the tumor microenvironment. Although increasing
metal loading can improve catalytic activity, the quandary of high metal content
versus potential systemic biotoxicity remains challenging. Here, a fully
exposed active site strategy by site-specific anchoring of single iridium (Ir)
atoms on the outer surface of a nitrogen-doped carbon composite (Ir singleatom
catalyst (SAC)) is reported to achieve remarkable catalytic performance
at ultralow metal content (≈0.11%). The Ir SAC exhibits prominent dual
enzymatic activities to mimic peroxidase and glutathione peroxidase, which
catalyzes the conversion of endogenous H_2O_2 into •OH in the acidic TME
and depletes glutathione (GSH) simultaneously. With an advanced support of
GSH-trapping platinum(IV) and encapsulation with a red-blood-cell membrane,
this nanocatalytic agent (Pt@IrSAC/RBC) causes intense lipid peroxidation
that boosts tumor cell ferroptosis. The Pt@IrSAC/RBC demonstrates
superior therapeutic efficacy in a mouse triple-negative mammary carcinoma
model, resulting in complete tumor ablation in a single treatment session
with negligible side effects. These outcomes may provide valuable insights
into the design of nanocatalysts with high performance and biosafety for
biomedical applications.
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摘要 :
Chemodynamic therapy, which produces cytotoxic hydroxyl radicals through intratumoral Fenton reactions, has been extensively explored in nanomedicine for cancer treatment. However, the limited endogenous hydrogen peroxide (H2O2) l...
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Chemodynamic therapy, which produces cytotoxic hydroxyl radicals through intratumoral Fenton reactions, has been extensively explored in nanomedicine for cancer treatment. However, the limited endogenous hydrogen peroxide (H2O2) levels, which serve as the reactant, weakens the anticancer effect of the Fenton reaction. In this work, a cascade catalytically reactive nanosystem has been constructed for the treatment of epithelial and embryonal tumors with high synergetic efficacy through the integration of natural glucose oxidase (GOD) and polyethylene glycol (PEG) onto the surface of Fe3S4 nanoplates (abbreviated as Fe3S4-PEG-GOD NPs). The GOD component consumes glucose in tumor and produces a large amount of H2O2, which provides rich substrates for the Fenton reaction catalyzed by the Fe catalytic center of the nanoplates. The intriguing photothermal conversion efficiency (45%) of the constructed composite nanocatalysts in the second near infrared (NIR-II) biowindow allows for photothermal treatment to substantially strengthen and synergize the anticancer effects of nanocatalysts both in vitro and in vivo. This synergy occurs through generation of a hyperthermic effect necessary for promoting the sequential catalytic reaction. The synergistic anticancer effect has been verified in both epithelial and embryonal tumor mouse models, and provides justification for the biomedical use of multifunctional nanocatalysts for versatile tumor nanotherapeutics.
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Those responsible for the development of sonosensitizers are faced with a dilemma between high sonosensitization efficacy and good biosecurity that limited the development of sonodynamic therapy (SDT). Herein, inspired by the intr...
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Those responsible for the development of sonosensitizers are faced with a dilemma between high sonosensitization efficacy and good biosecurity that limited the development of sonodynamic therapy (SDT). Herein, inspired by the intriguing therapeutic features of SDT and the potential catalytic activity of graphene quantum dots, the potential of N-doped graphene quantum dots(N-GQDs) to act as a sonosensitizer is demonstrated. The superior sonosensitization effect of N-GQDs is believed to be three to five times higher than that of traditional sonosensitizers (such as porphyrin, porphyrin Mn, porphyrin Zn, TiO_2, etc.). More importantly, the sonochemical mechanism of N-GQDs is revealed. Pyrrole N and pyridine N are believed to form catalytic centers in sonochemical processing of N-GQDs. This knowledge is important from the perspective of understanding the structure-dependent SDT enhancement of carbon nanostructure. Moreover, N-GQDs modified by folic acid(FA-N-GQDs) show a high marker rate for tumor cells (greater than 96%). Both in vitro and in vivo therapeutic results have exhibited high tumor inhibition efficiency (greater than 90%) of FA-N-GQDs as sonosensitizers while the oxidative stress response of tumor cells is activated through the PEX pathway and induced apoptosis via the p53 pathway.
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? 2022Nanozymes are artificial enzymes that mimic natural enzyme-like activities and show great promise for tumor catalytic therapy. However, new nanozymes with multiple catalytic activities for multifunctional nanotheranostic use...
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? 2022Nanozymes are artificial enzymes that mimic natural enzyme-like activities and show great promise for tumor catalytic therapy. However, new nanozymes with multiple catalytic activities for multifunctional nanotheranostic use remain challenging to design. Herein, for the first time, iron phthalocyanine (Fe(II)Pc) was assembled with poly(L-lactide-co-glycolide)-block-poly(ethylene glycol) to prepare an Fe(II)Pc assembly (denoted as Fe(II)Pc-A). The obtained Fe(II)Pc-A could be applied as a smart near-infrared (NIR) light-responsive nanotheranostic for simultaneous photoacoustic imaging-guided photothermal therapy. Notably, Fe(II)Pc-A possessed peroxidase, catalase, and oxidase mimicking activities, which could not only catalyze the conversion of intratumoral H2O2 to ?OH, but also degrade H2O2 to generate O2 and continuously catalyze the conversion of O2 to cytotoxic O2?-. Impressively, the dual reactive oxygen species (ROS) generation of Fe(II)Pc-A was further remarkably enhanced by the endogenous acidity of the tumor microenvironment and the exogenous NIR light-responsive photothermal effect. Moreover, the O2 self-supplying ability of Fe(II)Pc-A led to increased generation of O2?- for enhancing catalytic therapy in hypoxic tumor. These collective properties of Fe(II)Pc-A nanozyme enabled it to be a dual ROS generation accelerator for photothermally enhanced tumor catalytic therapy. Thus, a new type of high-performance nanozyme for multifunctional nanotheranostic use toward cancer was presented.
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? 2022 Acta Materialia Inc.The field of nanomedicine-catalyzed tumor therapy has achieved a lot of progress; however, overcoming the limitations of the tumor microenvironment (TME) to achieve the desired therapeutic effect remains...
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? 2022 Acta Materialia Inc.The field of nanomedicine-catalyzed tumor therapy has achieved a lot of progress; however, overcoming the limitations of the tumor microenvironment (TME) to achieve the desired therapeutic effect remains a major challenge. In this study, a nanocomposite hydrogel (GH@LDO) platform combining the nanozyme CoMnFe-layered double oxides (CoMnFe-LDO) and natural enzyme glucose oxidase (GOX) was engineered to remodel the TME to enhance tumor catalytic therapy. The CoMnFe-LDO is a nanozyme that can convert endogenous H2O2 into reactive oxygen species (ROS) and O2 to achieve chemodynamic therapy (CDT) and alleviate the hypoxic microenvironment. Meanwhile, GOX can catalyze the conversion of glucose and O2 to gluconic acid and H2O2, which not only represses the ATP production of tumor cells to achieve starvation therapy (ST), but also decreases the pH value of TME and supplies extra H2O2 to enhance the CDT effect. Furthermore, this well-designed CoMnFe-LDO possessed a high photothermal conversion efficiency of GH@LDO (66.63%), which could promote the generation of ROS to enhance the CDT effect and achieve photothermal therapy (PTT) under near-infrared light irradiation. The GH@LDO hydrogel performes cascade reaction which overcomes the limitation of the TME and achieves satisfactory CDT/ST/PTT synergetic effects in vitro and in vivo. This work provides a new strategy for remodeling the TME using nanomedicine to achieve precise tumor cascaded catalytic therapy. Statement of significance: At present, the focus of tumor therapy has begun to shift from monotherapy to combination therapy for improving the overall therapeutic effect. In this study, we synthesized a CoMnFe-LDO nanozyme composed of multiple transition metal oxides, which demonstrated improved peroxidase and oxidase activities as well as favorable photothermal conversion capability. The CoMnFe-LDO nanozyme was compounded with an injectable GH hydrogel crosslinked by GOX and horseradish peroxidase (HRP). This nanocomposite hydrogel overcame the limitations of weak acidity, H2O2, and O2 levels in the TME and achieved synergetic CDT, ST, and PTT effects based on the cascaded catalytic actions of CoMnFe-LDO and GOX to H2O2 and glucose.
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Nanozymes are nanomaterials with enzyme-like characteristics. As a new generation of artificial enzymes, nanozymes have the advantages of low cost, good stability, simple preparation, and easy storage, allowing them to overcome ma...
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Nanozymes are nanomaterials with enzyme-like characteristics. As a new generation of artificial enzymes, nanozymes have the advantages of low cost, good stability, simple preparation, and easy storage, allowing them to overcome many of the limitations of natural enzymes in enzymatic therapy. Currently, most reported nanozymes exhibit oxidoreductase-like activities and can regulate redox balance in cells. Nanozymes with superoxide dismutase and catalase activity can be used to scavenge reactive oxygen species (ROS) for cell protection, while those with peroxidase and oxidase activity can generate ROS to kill harmful cells, such as tumor cells and bacteria. In this review, we summarize recent progress in nanozyme-based medicine for enzymatic therapy and highlight the opportunities and challenges in this field for future study.
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摘要 :
Reactive oxygen species (ROS)-mediated tumor catalytic therapy is typically
hindered by gap junction proteins that form cell-to-cell channels to remove
cytotoxic ROS, thereby protecting tumor cells from oxidative damage. In this...
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Reactive oxygen species (ROS)-mediated tumor catalytic therapy is typically
hindered by gap junction proteins that form cell-to-cell channels to remove
cytotoxic ROS, thereby protecting tumor cells from oxidative damage. In this
work, a multifunctional nanozyme, FePGOGA, is designed and prepared by
Fe(III)-mediated oxidative polymerization (FeP), followed by glucose oxidase
(GOx) and GAP19 peptides co-loading through electrostatic and π-π interactions.
The FePGOGA nanozyme exhibits excellent cascade peroxidase- and
glutathione-oxidase-like activities that efficiently catalyze hydrogen peroxide
conversion to hydroxyl radicals and convert reduced glutathione to oxidized
glutathione disulfide. The loaded GOx starves the tumors and aggravates
tumor oxidative stress through glucose decomposition, while GAP19 peptides
block the hemichannels by inducing degradation of Cx43, thus increasing the
accumulation of intracellular ROS, and decreasing the transport of intracellular
glucose. Furthermore, the ROS reacts with primary amines of heat shock
proteins to destroy their structure and function, enabling tumor photothermal
therapy at the widely sought-after mild temperature (mildPTT, ≤45 °C). In
vivo experiments demonstrate the significant antitumor effectof FePGOGA
on cal27 xenograft tumors under near-infrared light irradiation. This study
demonstrates the successful ablation of gap junction proteins to overcome
resistance to ROS-mediated therapy, providing a regulator to suppress tumor
self-preservation during tumor starvation, catalytic therapy, and mildPTT.
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Abstract The existence of natural van der Waals gaps in layered materials allows them to be easily intercalated with varying guest species, offering an appealing strategy to optimize their physicochemical properties and applicatio...
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Abstract The existence of natural van der Waals gaps in layered materials allows them to be easily intercalated with varying guest species, offering an appealing strategy to optimize their physicochemical properties and application performance. Herein, we report the activation of layered MoO3 nanobelts via aqueous intercalation as an efficient biodegradable nanozyme for tumor‐specific photo‐enhanced catalytic therapy. The long MoO3 nanobelts are grinded and then intercalated with Na+ and H2O to obtain the short Na+/H2O co‐intercalated MoO3?x (NH?MoO3?x) nanobelts. In contrast to the inert MoO3 nanobelts, the NH?MoO3?x nanobelts exhibit excellent enzyme‐mimicking catalytic activity for generation of reactive oxygen species, which can be further enhanced by the photothermal effect under a 1064?nm laser irradiation. Thus, after bovine serum albumin modification, the NH?MoO3?x nanobelts can efficiently kill cancer cells in vitro and eliminate tumors in vivo facilitating with 1064?nm laser irradiation.
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摘要 :
Tumor-activatable ultrasmall nanozyme generation is an unprecedented strategy to overcome intrinsically fatal defects of traditional reactive oxygen species (ROS)-based nanoagents for deep tumor penetration, including limited tiss...
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Tumor-activatable ultrasmall nanozyme generation is an unprecedented strategy to overcome intrinsically fatal defects of traditional reactive oxygen species (ROS)-based nanoagents for deep tumor penetration, including limited tissue-penetrating depth of external energy, heavy reliance on oxygen and nonspecific toxicity of therapeutic agents. Here, based on the cascade reaction between glucose oxidase (GOx) and ultrasmall peroxidase nanozyme embedded into acid-dissociable zeolitic imidazolate framework-8 (ZIF-8), such a tumor-activatable ultrasmall nanozyme generator is designed for enhanced penetration and deep catalytic therapy. With the aid of mildly acidic tumor microenvironment, the produced gluconic acid from intratumoral glucose can gradually induce the dissociation of ZIF-8 to release ultrasmall peroxidase nanozyme with significant intratumoral penetration. On the other hand, the generated hydrogen peroxide with relatively long-life can be subsequently catalyzed by penetrated pemxidase nanozyme into toxic hydroxyl radicals for deep catalytic therapy. In this way, the well-designed nanoplatform not only can greatly enhance tumor penetration but also directly induce exogenous ROS without oxygen participation and external energy input, thereby thoroughly avoiding the inactivation of traditional ROS-based nanoagents in the extremely hypoxic tumor center and finally resulting in remarkable deep catalytic therapy.
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As an indispensable strategy for tumor treatment, surgery may cause two
major challenges: tumor recurrence and wound infection. Here, a thermoelectric
therapeutic strategy is provided as either an independent cancer
therapy or ...
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As an indispensable strategy for tumor treatment, surgery may cause two
major challenges: tumor recurrence and wound infection. Here, a thermoelectric
therapeutic strategy is provided as either an independent cancer
therapy or surgical adjuvant treatment. Bi_(0.5)Sb_(1.5)Te_3 (BST) and Bi_2Te_(2.8)Se_(0.2)
(BTS) nanoplates composed of Z-scheme thermoelectric heterojunction
(BST/BTS) are fabricated via a two-step hydrothermal processes. The
contact between BST and BTS constructs an interfacial electric field due to
Fermi energy level rearrangement, guiding electrons in the conductive band
(CB) of BTS combine with the holes in the valance band (VB) of BST, leaving
stronger reduction/oxidation potentials of electrons and holes in the CB
of BST and the VB of BTS. Moreover, under a mild temperature gradient,
another self-built-in electric field is formed facilitating the migration of
electrons and holes to their surfaces. Based on the PEGylated BST/BTS heterojunction,
a novel thermoelectric therapy platform is developed through
intravenous injection of BST/BTS and external cooling of the tumors. This
thermoelectric strategy is also proved effective for combination cancer
therapy with β-elemene. Moreover, the combination of heterojunction and
hydrogel is administrated on the wound after surgery, achieving efficient
residual tumor treatment and antibacterial effects.
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