Traditional tumor treatments, including chemotherapy, radiotherapy, photodynamic therapy, and photothermal therapy, are developed and used to treat different types of cancer. Recently, chemodynamic ...therapy (CDT) has been emerged as a novel cancer therapeutic strategy. CDT utilizes Fenton or Fenton‐like reaction to generate highly cytotoxic hydroxyl radicals (•OH) from endogenous hydrogen peroxide (H2O2) to kill cancer cells, which displays promising therapeutic potentials for tumor treatment. However, the low catalytic efficiency and off‐target side effects of Fenton reaction limit the biomedical application of CDT. In this regard, various strategies are implemented to potentiate CDT against tumor, including retrofitting the tumor microenvironment (e.g., increasing H2O2 level, decreasing reductive substances, and reducing pH), enhancing the catalytic efficiency of nanocatalysts, and other strategies. This review aims to summarize the development of CDT and summarize these recent progresses of nanocatalyst‐mediated CDT for antitumor application. The future development trend and challenges of CDT are also discussed.
Chemodynamic therapy (CDT) can produce highly lethal hydroxyl free radicals via Fenton or Fenton‐like reaction. This review summarizes recent progress of nanocatalyst‐mediated CDT for antitumor application, highlights various strategies to improve the catalytic efficiency, and discusses the challenges and opportunities of CDT in the future.
Here, a Mn(III)-sealed metal–organic framework (MOF) nanosystem based on coordination between Mn(III) and porphyrin (TCPP) via a one-pot method was designed and constructed. Mn(III), as a sealer, ...not only quenched TCPP-based fluorescence but also inhibited reactive oxygen species (ROS) generation, which made MOFs an “inert” theranostic nanoparticle. Interestingly, upon endocytosis by tumor cells, MOFs were disintegrated into Mn(II) and free TCPP by intracellular glutathione (GSH) in tumor cells, owing to redox reaction between Mn(III) and GSH. This disintegration would lead to consumption of antioxidant GSH and activated Mn(II)-based magnetic resonance imaging (MRI) as well as TCPP-based fluorescent imaging. More importantly, such a GSH-regulated TCPP release could implement controllable ROS generation under irradiation, which avoided side effects (inflammation and damage of normal tissues). As a consequence, after unlocking by GSH, Mn(III)-sealed MOFs could significantly improve the therapeutic efficiency of photodynamic therapy by combining controlled ROS generation and GSH depletion after precise dual tumor homing.
Modulating tumor microenvironment to amplify the therapeutic efficiency would be a novel strategy for effective cancer treatment. In this work, based on the TPZ-loaded porphyrinic metal organic ...framework PCN-224 (PCN stands for porous coordination network), a cancer cell membrane-coated nanoplatform (TPZ@PCN@Mem) was fabricated for tumor targeted PDT and the successively resulting hypoxia-amplified bioreductive therapy. After administration, TPZ@PCN@Mem exhibited the selective accumulation and long-term retention at tumor tissue due to the immune escape and homologous targeting endowed by the cancer membrane coating. Upon light irradiation, PCN-224-mediated toxic reactive oxygen species (ROS) were generated for PDT, and the resulting local hypoxia microenvironment would further accelerate the activation of TPZ for enhanced chemotherapy in 4T1 orthotopic tumor. The cascade synergistic therapeutic effects of TPZ@PCN@Mem could significantly suppress the primary tumor growth, and also inhibit its distal metastasis with minimal side effects. The study indicated an overwhelming superiority of utilizing this bioinspired strategy for tumor targeted PDT and hypoxia-activated bioreductive therapy, which provided a new insight for precise and effective tumor treatment.
Information processing with optoelectronic devices provides an alternative way to efficiently process hybrid optical and electronic signals. Ferroelectric field‐effect transistors (FeFETs) can ...effectively respond to external optical and electrical stimuli by modulating their polarization states. Here, a 2D FeFET is demonstrated by the epitaxial growth of high‐quality 2D bismuth layered oxyselenide (Bi2O2Se) films on PMN‐PT(001) ferroelectric single‐crystal substrates. Upon switching the polarization direction of PMN‐PT, the authors realize in situ, reversible, and nonvolatile manipulation of the resistance of Bi2O2Se thin film (≈877%). The device simultaneously exhibits a polarization‐dependent photoresponse through visible light (λ = 405 nm) and infrared light (IR, λ = 980 nm) illumination. Combining optical stimuli with ferroelectric gating, it is demonstrated that the devices not only show nonvolatile memory and optoelectronic responses, but also show coincidence detection of visible and IR light. This work holds great potential in constructing new multiresponse and multifunction 2D‐FeFETs.
2D ferroelectric field‐effect transistors devices are fabricated by epitaxial growth of Bi2O2Se on Pb(Mg1/3Nb2/3)O3‐PbTiO3. The devices exhibit ferroelectric polarization‐dependent photoresponse upon visible light (λ = 405 nm) and infrared light (IR, λ = 980 nm) illumination. Combining optical stimuli with ferroelectric gating, the devices show not only nonvolatile memory and optoelectronic response, but also coincidence detection of visible and infrared light.
This study reports a tumor-specific ROS-responsive nanoplatform capable of the combination of nitric oxide (NO)-based gas therapy and sensitized photodynamic therapy (PDT). The nanoplatform is ...constructed on porous coordination network (PCN), which contains NO donor L-Arg and is concurrently coated with cancer cell membrane (L-Arg@PCN@Mem). Under near infrared light (NIR) irradiation, L-Arg@PCN@Mem produces plenty of reactive oxygen species (ROS) directly for PDT therapy, while a part of ROS take the role of oxidative to converse L-Arg into NO for combined gas therapy. The results indicate that the transformation of ROS to NO can enhance PDT efficacy in hypoxic tumors owing to the ability of NO in freely diffusing into deep hypoxic tumor site. Moreover, homologous targeting function originated from the coating of cancer cells membrane further improves the tumor treatment effect owing to the biotargeting toward homologous tumors. This L-Arg@PCN@Mem nanoplatform provides a new therapy paradigm of overcoming the hypoxia barrier of tumor therapy, and holds great potential for the treatment of tumor and NO-related diseases.
A ROS-responsive L-Arg@PCN@Mem nanoplatform was prepared for NO-based gas therapy and NO-sensitized photodynamic therapy (PDT). This nanoplatform displayed synergistic effect to increase tumor oxidative/nitrification stress and suppress growth and proliferation of cancer cells with negligible side effects. Display omitted
The age-dependent decline in remyelination potential of the central nervous system during ageing is associated with a declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). The ...molecular players that can enhance OPC differentiation or rejuvenate OPCs are unclear. Here we show that, in mouse OPCs, nuclear entry of SIRT2 is impaired and NAD
levels are reduced during ageing. When we supplement β-nicotinamide mononucleotide (β-NMN), an NAD
precursor, nuclear entry of SIRT2 in OPCs, OPC differentiation, and remyelination were rescued in aged animals. We show that the effects on myelination are mediated via the NAD
-SIRT2-H3K18Ac-ID4 axis, and SIRT2 is required for rejuvenating OPCs. Our results show that SIRT2 and NAD
levels rescue the aged OPC differentiation potential to levels comparable to young age, providing potential targets to enhance remyelination during ageing.
A multifunctional prodrug, designated as TPP‐L‐GEM, is fabricated to realize image‐guided in situ tumor photodynamic therapy (PDT) with red light activatable chemotherapy. Gemcitabine is conjugated ...with a fluorescent photosensitizer, meso‐tetraphenylporphyrin (TPP), by a reactive oxygen species cleavable thioketal linker. Under the irradiation of low‐energy red light, TPP can generate singlet oxygen and damage tumor cells by photodynamic therapy. Simultaneously, the thioketal linkage can be cleaved by singlet oxygen and result in a cascaded gemcitabine release, causing sustained cell damage by chemotherapy. With the combination of PDT and cascaded chemotherapy, TPP‐L‐GEM shows significant tumor therapeutic efficacy in vitro and in vivo. Furthermore, the inherent fluorescent property of TPP endows the TPP‐L‐GEM prodrug with noninvasive drug tracking capability, which is favorable for image‐guided tumor therapy.
A red light activatable multifunctional prodrug is fabricated to realize in situ tumor photodynamic therapy (PDT) with cascaded chemotherapy. This multifunctional prodrug demonstrates a new strategy for image‐guided combination therapy of PDT with cascaded chemotherapy.
As an essential path toward the elucidation of the reaction mechanism, the capture of the catalytically active phase and its evolution has been the primary goal of mechanistic studies. Here, the ...physicochemical properties on In2O3 (111) and Pt/In2O3 (111) thin film model catalysts were tracked in CO2 hydrogenation atmosphere under various pressures and temperatures by ambient pressure X‐ray photoelectron spectroscopy (APXPS). The redox behaviours of surface Pt and In2O3, the formation and interconversion of reaction intermediates, and the structural dynamics at the topmost surface, as a consequence of the outward diffusion of InOx species, nucleation of surface Pt nanostructures and the formation of PtInOx species, were captured and analyzed. The reconstruction at the Pt/In2O3 (111) interface was also observed by time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) and scanning electron microscopy (SEM) analysis. In‐situ spectroscopic and structural analysis on a well‐defined metal/metal‐oxide interface offers a powerful means to probe the mechanistic details of the heterogeneous processes.
Mechanistic details of the metal/metal‐oxide interface for heterogeneous processes: The surface physicochemical properties of In2O3 (111) and Pt/In2O3 (111) were investigated using ambient pressure X‐ray photoelectron spectroscopy in the atmosphere of CO2 hydrogenation reaction, including redox behaviors of surface Pt and In2O3, the formation and interconversion of reaction intermediates. Dynamic interfacial reconstruction was observed and demonstrated by SEM and 3D topological elemental mappings using ToF‐SIMS.
A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS ...coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chemodynamic therapy (CDT) can efficiently destroy tumor cells via Fenton reaction in the presence of H
O
and a robust catalyst. However, it has faced severe challenges including the limited amounts ...of H
O
and inefficiency of catalysts. Here, an adenosine triphosphate (ATP)-responsive autocatalytic Fenton nanosystem (GOx@ZIF@MPN), incorporated with glucose oxidase (GOx) in zeolitic imidazolate framework (ZIF) and then coated with metal polyphenol network (MPN), was designed and synthesized for tumor ablation with self-supplied H
O
and TA-mediated acceleration of Fe(III)/Fe(II) conversion. In the ATP-overexpressed tumor cells, the outer shell MPN of GOx@ZIF@MPN was degraded into Fe(III) and tannic acid (TA) and the internal GOx was exposed. Then, GOx reacted with the endogenous glucose to produce plenty of H
O
, and TA reduced Fe(III) to Fe(II), which is a much more vigorous catalyst for the Fenton reaction. Subsequently, self-produced H
O
was catalyzed by Fe(II) to generate highly toxic hydroxyl radical (•OH) and Fe(III). The produced Fe(III) with low catalytic activity was quickly reduced to reactive Fe(II) mediated by TA, forming an accelerated Fe(III)/Fe(II) conversion to guarantee efficient Fenton reaction-mediated CDT. This autocatalytic Fenton nanosystem might provide a good paradigm for effective tumor treatment.
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