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1.
Adv Healthc Mater ; : e2402079, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225409

RESUMEN

Mild-temperature photothermal therapy (mild-PTT, 42-45 °C) offers a higher level of biosafety. However, its therapeutic effects are compromised by the heat shock response (HSR), a cellular self-defense mechanism, which triggers the overexpression of heat shock proteins (HSPs) with the capacity of repairing the damaged tumor cells. Herein, this work fabricates a novel nanoreactor by incorporating up-conversion nanoparticles (UCNPs), chlorin e6 (Ce6), and glucose oxidase (GOx) onto the ultrathin black phosphorus nanosheet (BPNS) (denoted as GOx-BUC). This nanoreactor amplifies mild-PTT effects under irradiation with an 808 nm laser, modulating HSPs-mediated cellular self-defense fate. On one hand, upon irradiation with a 980 nm laser, UCNPs can transfer energy to excite Ce6, leading to the generation of ROS burst, which achieves indiscriminate damage to HSPs activity in deeper tumor tissues. On the other hand, GOx can consume glucose, thereby depleting the ATP energy supply and further suppressing HSPs expression. Consequently, GOx-BUC exhibits excellent anti-tumor efficacy under mild temperature in a human colorectal cancer mouse model, resulting in complete tumor inhibition with negligible side effects. This black phosphorous nanoreactor, featuring dual-track HSPs destruction functionality, introduces novel perspectives for enhancing mild-PTT effectiveness while maintaining high biosafety.

2.
ACS Nano ; 18(37): 25740-25753, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39226211

RESUMEN

Enzyme nanoreactors are nanoscale compartments consisting of encapsulated enzymes and a selectively permeable barrier. Sequestration and colocalization of enzymes can increase catalytic activity, stability, and longevity, highly desirable features for many biotechnological and biomedical applications of enzyme catalysts. One promising strategy to construct enzyme nanoreactors is to repurpose protein nanocages found in nature. However, protein-based enzyme nanoreactors often exhibit decreased catalytic activity, partially caused by a mismatch of protein shell selectivity and the substrate requirements of encapsulated enzymes. No broadly applicable and modular protein-based nanoreactor platform is currently available. Here, we introduce a pore-engineered universal enzyme nanoreactor platform based on encapsulins-microbial self-assembling protein nanocompartments with programmable and selective enzyme packaging capabilities. We structurally characterize our protein shell designs via cryo-electron microscopy and highlight their polymorphic nature. Through fluorescence polarization assays, we show their improved molecular flux behavior and highlight their expanded substrate range via a number of proof-of-concept enzyme nanoreactor designs. This work lays the foundation for utilizing our encapsulin-based nanoreactor platform for diverse future biotechnological and biomedical applications.


Asunto(s)
Ingeniería de Proteínas , Porosidad , Nanotecnología , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Biocatálisis , Tamaño de la Partícula
3.
Front Bioeng Biotechnol ; 12: 1443843, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280341

RESUMEN

Epithelial cell adhesion molecule negative circulating tumor cells (EpCAM- CTCs) and EpCAM positive CTCs (EpCAM + CTCs) have different biological characteristics. Therefore, the isolation of EpCAM + CTCs and EpCAM- CTCs is a new strategy to study the heterogeneity of tumor cells. The azobenzene group (Azo) and cyclodextrin (CD) composite system forms a photosensitive molecular switch based on the effect of external light stimulation. We used the technology of specifically capturing CTCs using anti-EpCAM and aptamers functionalized nanochips. Both anti-EpCAM and aptamers can be connected to Azo through the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) modification process. Therefore, we assume that a photosensitive intelligent nanoreactor (PSINR) modified with anti-EpCAM can be used to capture EpCAM + CTCs; Utilizing the characteristics of aptamer and ligand binding, a PSINR modified with aptamer is used to capture EpCAM- CTCs; Then, two PSINRs were separated and stimulated with light to release EpCAM + CTCs and EpCAM- CTCs, respectively. Based on the isolation the EpCAM + CTCs and EpCAM- CTCs, we expected to reveal the key biological mechanisms of tumor recurrence, metastasis and drug resistance, and make the individualized treatment of liver cancer more targeted, safe and effective, and provide a new basis for the final realization of accurate and individualized treatment of tumors.

4.
Small ; : e2404018, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39133083

RESUMEN

The designed and ordered co-immobilization of multiple enzymes for vectorial biocatalysis is challenging. Here, a combination of protein phase separation and bioorthogonal linking is used to generate a zeolitic imidazole framework (ZIF-8) containing co-immobilized enzymes. Zn2+ ions induce the clustering of minimal protein modules, such as 6-His tag, proline-rich motif (PRM) and SRC homology 3 (SH3) domains, and allow for phase separation of the coupled aldoketoreductase (AKR) and alcohol dehydrogenase (ADH) at low concentrations. This is achieved by fusing SpyCatcher and PRM-SH3-6His peptide fragments to the C and N termini of AKR, respectively, and the SpyTag to ADH. Addition of 2-methylimidazole results in droplet formation and enables in situ spatial embedding the recombinant AKR and ADH to generate the cascade biocalysis system encapsulated in ZIF-8 (AAE@ZIF). In synthesizing (S)-1-(2-chlorophenyl) ethanol, ater 6 cycles, the yield can still reach 91%, with 99.99% enantiomeric excess (ee) value for each cycle. However, the yield could only reach 72.9% when traditionally encapsulated AKR and ADH in ZIF-8 are used. Thus, this work demonstrates that a combination of protein phase separation and bio-orthogonal linking enables the in situ creation of a stable and spatially organized bi-enzyme system with enhanced channeling effects in ZIF-8.

5.
Adv Mater ; : e2409188, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210633

RESUMEN

Constructing nanoreactors with multiple active sites in well-defined crystalline mesoporous frameworks is an effective strategy for tailoring photocatalysts to address the challenging of CO2 reduction. Herein, one-dimensional (1-D) mesoporous single-crystal TiO2 nanorod (MS-TiO2-NRs, ≈110 nm in length, high surface area of 117 m2 g-1, and uniform mesopores of ≈7.0 nm) based nanoreactors are prepared via a droplet interface directed-assembly strategy under mild condition. By regulating the interfacial energy, the 1-D mesoporous single-crystal TiO2 can be further tuned to polycrystalline fan- and flower-like morphologies with different oxygen vacancies (Ov). The integration of single-crystal nature and mesopores with exposed oxygen vacancies make the rod-like TiO2 nanoreactors exhibit a high-photocatalytic CO2 reduction selectivity to CO (95.1%). Furthermore, photocatalytic cascade nanoreactors by in situ incorporation of CuW6O24 (W-Cu) clusters onto MS-TiO2-NRs via Ov are designed and synthesized, which improved the CO2 adsorption capacity and achieved two-step CO2-CO-CH4 photoreduction. The second step CO-to-CH4 reaction induced by W-Cu sites ensures a high generation rate of CH4 (420.4 µmol g-1 h-1), along with an enhanced CH4 selectivity (≈94.3% electron selectivity). This research provides a platform for the design of mesoporous single-crystal materials, which potentially extends to a range of functional ceramics and semiconductors for various applications.

6.
Biomaterials ; 311: 122702, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39008916

RESUMEN

The blood-brain barrier (BBB) is a complex and highly restrictive barrier that prevents most biomolecules and drugs from entering the brain. However, effective strategies for delivering drugs to the brain are urgently needed for the treatment of glioblastoma. Based on the efficient BBB penetration properties of exosomes derived from brain metastatic breast cancer cells (EB), this work prepared a nanoreactor (denoted as MAG@EB), which was constructed by self-assembly of Mn2+, arsenate and glucose oxidase (GOx) into nanoparticles wrapped with EB. MAG@EB can enhance the efficiency of traversing the BBB, target and accumulate at in situ glioblastoma sites. The GOx-driven glycolysis effectively cuts off the glucose supply while also providing an abundance of H2O2 and lowering pH. Meanwhile, the released Mn2+ mediated Fenton-like reaction converts elevated H2O2 into highly toxic ·OH. Besides, AsV was reduced to AsIII by glutathione, and the tumor suppressor gene P53 was activated by AsIII to kill glioblastoma cells. Glioblastoma succumbed to the redox cascade triggered by MAG@EB, as the results demonstrated in vivo and in vitro, yielding a remarkable therapeutic effect. This work provides a promising therapeutic option mediated by cascaded nanoreactors for the future treatment of glioblastoma.


Asunto(s)
Barrera Hematoencefálica , Neoplasias Encefálicas , Glioblastoma , Glucosa Oxidasa , Oxidación-Reducción , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/metabolismo , Barrera Hematoencefálica/metabolismo , Humanos , Animales , Línea Celular Tumoral , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Glucosa Oxidasa/metabolismo , Peróxido de Hidrógeno/metabolismo , Nanopartículas/química , Ratones , Ratones Desnudos , Catálisis , Ratones Endogámicos BALB C
7.
Angew Chem Int Ed Engl ; : e202411255, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980971

RESUMEN

Conversion-type electrode materials have gained massive research attention in sodium-ion batteries (SIBs), but their limited reversibility hampers practical use. Herein, we report a bifunctional nanoreactor to boost highly reversible sodium-ion storage, wherein a record-high reversible degree of 85.65 % is achieved for MoS2 anodes. Composed of nitrogen-doped carbon-supported single atom Mn (NC-SAMn), this bifunctional nanoreactor concurrently confines active materials spatially and catalyzes reaction kinetics. In situ/ex situ characterizations including spectroscopy, microscopy, and electrochemistry, combined with theoretical simulations containing density functional theory and molecular dynamics, confirm that the NC-SAMn nanoreactors facilitate the electron/ion transfer, promote the distribution and interconnection of discharging products (Na2S/Mo), and reduce the Na2S decomposition barrier. As a result, the nanoreactor-promoted MoS2 anodes exhibit ultra-stable cycling with a capacity retention of 99.86 % after 200 cycles in the full cell. This work demonstrates the superiority of bifunctional nanoreactors with two-dimensional confined and catalytic effects, providing a feasible approach to improve the reversibility for a wide range of conversion-type electrode materials, thereby enhancing the application potential for long-cycled SIBs.

8.
Chemistry ; : e202402197, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38923156

RESUMEN

Since their discovery, clathrate hydrates (CHs) have received great attention both from theoretical and experimental aspects due to their great potential for gas storage and prospective applications as icy crystal materials. However, there has been limited research on the decomposition, reduction or other reactions of gases enclosed in CHs. Thanks to their unique hydrogen bonding network and cavity structures, CHs can serve as the promising nanoreactors to achieve chemical conversions, e. g. reducing greenhouse gases. In this review-type article, we characterize the potential performance of such CHs nanoreactors by discussing their multiple functions including important roles of hydrogen bonds in CHs, e. g. the confinement effect and proton source, and then discuss the enhanced electron-binding ability of guest molecules and the structures and properties of trapped electrons in the stacked nanocages, which contribute to our understanding of chemical reactions occurring in CHs. Finally, we provide detailed analyses of representative reaction mechanisms underwent in CH nanoreactors and effective calculational and molecular dynamics simulation methods. This review-type article aims to provide a detailed summary about the functional characteristics of CHs and reactivity in CHs, which make CHs a kind of promising icy nanoreactors.

9.
ACS Appl Bio Mater ; 7(7): 4611-4621, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38920441

RESUMEN

Glucose oxidase (GOx) selectively oxidizes ß-d-glucose into gluconic acid and hydrogen peroxide; thus, it has emerged as a promising anticancer agent by tumor starvation and oxidative therapy. Here, we developed a nanoscale platform or "nanoreactor" that incorporates GOx and the bioactive natural product curcumin (CUR) to achieve a multimodal anticancer nanocomposite. The composite nanoreactor was formed by loading CUR in biodegradable polymeric nanoparticles (NPs) of poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL). Prime-coating of the NPs with an iron(III)-tannic acid complex enabled facile immobilization of GOx on the NP surface. The NPs were monodisperse with a hydrodynamic diameter of 122 nm and a partially negative surface charge. The NPs were also associated with an excellent CUR loading efficiency and sustained release up to 96 h, which was accelerated by surface-immobilized GOx and followed supercase II transport. Viability assays were conducted on two model cancer cell lines, MCF-7 and MDA-MB-231 cells, as well as human dermal fibroblasts as a representative normal cell line. The assays revealed significantly improved potency of CUR in the composite nanoreactor, with up to 6000- and 1280-fold increase in MCF-7 and MDA-MB-231 cells, respectively, and lower toxicity toward normal cells. The NPs were also able to promote intracellular reactive oxygen species (ROS) generation and dissipation of the mitochondrial membrane potential, providing important clues on the mechanism of action of the nanoreactor. Further investigation of caspase-3 activity revealed that the nanoreactor had no effect or inhibited caspase-3 levels, signifying a caspase-independent mechanism of inducing apoptosis. Our findings present a promising nanocarrier platform that combines therapeutic agents with distinct mechanisms of action acting in synergy for more effective cancer therapy.


Asunto(s)
Antineoplásicos , Supervivencia Celular , Curcumina , Glucosa Oxidasa , Tamaño de la Partícula , Curcumina/farmacología , Curcumina/química , Humanos , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/química , Antineoplásicos/farmacología , Antineoplásicos/química , Supervivencia Celular/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Ensayo de Materiales , Nanopartículas/química , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Nanocompuestos/química , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo
10.
Adv Mater ; 36(31): e2403865, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38857624

RESUMEN

High-entropy alloy (HEA) nanostructures arranged into well-defined configurations hold great potential for accelerating the development of electronics, photonics, catalysis, and device integration. However, the random nucleation induced by the disparity in physicochemical properties of multiple elements makes it challenging to achieve single-particle synthesis at the patterned preset sites in the high-entropy scenario. Herein, the liquid metal nanoreactor strategy is proposed to realize the construction of HEA arrays. The coalescence of the liquid metal driven by the tendency to decrease surface energy provides a restricted environment for the nucleation and growth to form single HEA particles at the preset locations, which can be regarded as a self-confinement reaction. Liquid metal endowing a low diffusion energy barrier on the substrate and a high diffusivity of the alloy system can dynamically promote the aggregation process. As a result, the HEA array is prepared with elements up to eleven and possesses uniform periodicity, which exhibits excellent holography response in a broad spectrum. This work injects new vitality into the construction of HEA nanopatterns and provides an excellent platform for propelling their fundamental research and applications.

11.
ACS Nano ; 18(24): 15638-15650, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38848453

RESUMEN

For practical application of lithium-sulfur batteries (LSBs), designing devices with an overall optimal structure instead of modifying electrode materials is significant. Herein, we report a chip-inspired design of a vertically integrated structure as an LSB cathode by implanting Mo2C nanoparticles and nanosulfur into the reduced graphene oxide (rGO) matrix. This configuration enabled the synthesis of isolated sulfur nanoreactors (S-NRs) integrated in a tandem array on the rGO, generating chip-like integrated LSBs. The spatial confinement/protection and concentration gradient of the S-NRs effectively avoided the dissolution, diffusion, and loss of polysulfides, thereby enhancing the sulfur utilization and redox reaction kinetics. Additionally, the adaptive storage energy can be improved by utilizing the tandem, isolation, and synergistic multiplicative effect among the nanoreactor units. As a result, the integrated LSB cathode obtained excellent electrochemical performances with an initial capacity of 1392 mAh g-1 at 0.1C, a low capacity decay rate of 0.017% per cycle during 1500 cycles of operation at 0.5C, and a superior rate performance. This work provides a rational design idea and method of further advancing the precise preparation of high-performance energy storage devices.

12.
Adv Sci (Weinh) ; 11(29): e2404143, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38785180

RESUMEN

Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real-time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self-adaptive hyperthermia supramolecular cascade nano-reactor ACFDG is constructed via one-step supramolecular self-assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS-inflammatory cascade through catalytic cascade reactions, up-regulate the expression of heat shock proteins (HSPs) under near-infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real-time non-invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano-reactor combined with PA imaging for real-time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.


Asunto(s)
Regeneración Ósea , Técnicas Fotoacústicas , Técnicas Fotoacústicas/métodos , Regeneración Ósea/fisiología , Animales , Diabetes Mellitus Experimental/terapia , Hipertermia Inducida/métodos , Modelos Animales de Enfermedad , Ratas , Humanos , Ratones
13.
Chembiochem ; 25(15): e202400346, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38775416

RESUMEN

Multi-enzyme cascade catalysis has become an important technique for chemical reactions used in manufacturing and scientific study. In this research, we designed a four-enzyme integrated catalyst and used it to catalyse the deracemization reaction of cyclic chiral amines, where monoamine oxidase (MAO) catalyses the enantioselective oxidation of 1-methyl-1,2,3,4-tetrahydroisoquinoline (MTQ), imine reductase (IRED) catalyses the stereo selective reduction of 1-methyl-3,4-dihydroisoquinoline (MDQ), formate dehydrogenase (FDH) is used for the cyclic regeneration of cofactors, and catalase (CAT) is used for decomposition of oxidative reactions. The four enzymes were immobilized via polydopamine (PDA)-encapsulated dendritic organosilica nanoparticles (DONs) as carriers, resulting in the amphiphilic core-shell catalysts. The hydrophilic PDA shell ensures the dispersion of the catalyst in water, and the hydrophobic DON core creates a microenvironment with the spatial confinement effect of the organic substrate and the preconcentration effect to enhance the stability of the enzymes and the catalytic efficiency. The core-shell structure improves the stability and reusability of the catalyst and rationally arranges the position of different enzymes according to the reaction sequence to improve the cascade catalytic performance and cofactor recovery efficiency.


Asunto(s)
Aminas , Monoaminooxidasa , Polímeros , Aminas/química , Aminas/metabolismo , Monoaminooxidasa/metabolismo , Monoaminooxidasa/química , Polímeros/química , Polímeros/metabolismo , Formiato Deshidrogenasas/metabolismo , Formiato Deshidrogenasas/química , Catalasa/química , Catalasa/metabolismo , Indoles/química , Indoles/metabolismo , Estereoisomerismo , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Oxidación-Reducción , Nanopartículas/química , Biocatálisis , Compuestos de Organosilicio/química , Oxidorreductasas/metabolismo , Oxidorreductasas/química , Catálisis
14.
Angew Chem Int Ed Engl ; : e202406065, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802982

RESUMEN

The catalytic process of Li2S formation is considered a key pathway to enhance the kinetics of lithium-sulfur batteries. Due to the system's complexity, the catalytic behavior is uncertain, posing significant challenges for predicting activity. Herein, we report a novel cascaded dual-cavity nanoreactor (NiCo-B) by controlling reaction kinetics, providing an opportunity for achieving hierarchical catalytic behavior. Through experimental and theoretical analysis, the multilevel structure can effectively suppress polysulfides dissolution and accelerate sulfur conversion. Furthermore, we differentiate the adsorption (B-S) and catalytic effect (Co-S) in NiCo-B, avoiding catalyst deactivation caused by excessive adsorption. As a result, the as-prepared battery displays high reversible capacity, even with sulfur loading of 13.2 mg cm-2 (E/S=4 µl mg-1), the areal capacity can reach 18.7 mAh cm-2.

15.
Angew Chem Int Ed Engl ; 63(31): e202406693, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-38781083

RESUMEN

Apart from electrode material modification, architecture design and optimization are important approaches for improving lithium-sulfur battery performance. Herein, an integrated structure with tandem connection is constructed by confining nanosulfur (NS) in conductive poly(3,4-ethylenedioxythiophene) (PEDOT) reaction chambers, forming an interface of discrete independent nanoreactor units bonded onto carbon nanotubes (noted as CNT/NS@PEDOT). The unique spatial confinement and concentration gradients of sulfur@PEDOT nanoreactors (SP-NRs) can promote reaction kinetics while facilitating rapid polysulfide transformation and minimizing dissolution and diffusion losses. Meanwhile, overall ultrahigh energy input and output are achieved through tandem connection with carbon nanotubes, isolation with PEDOT coating, and synergistic multiplicative effects among SP-NRs. As a result, it delivers a high initial discharge capacity of 1246 mAh g-1 at 0.1 C and 918 mAh g-1 at 1 C, the low capacity decay rate per lap of 0.011 % is achieved at a current density of 1 C after 1000 cycles. This research emphasizes the innovative structural design to provide a fresh trajectory for the further advancement of high-performance energy storage devices.

16.
Small ; : e2401335, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693088

RESUMEN

Exploration of multifunctional integrated catalysts is of great significance for photocatalysis toward practical application. Herein, a 1D confined nanoreactor with a heterogeneous core-shell structure is designed for synergies of efficient catalysis and temperature monitoring by custom encapsulation of Z-scheme heterojunction CuS quantum dots/BiVO4 (CuS QDs/BiVO4) and Y2O2S-Er, Yb. The dispersed active sites created by the QDs with high surface energy improve the mass transfer efficiency, and the efficient electron transport channels at the heterogeneous interface extend the carrier lifetime, which endows the nanoreactor with excellent catalytic performance. Meanwhile, real-time temperature monitoring is realized based on the thermally coupled levels 2H11/2/4S3/2→4I15/2 of Er3+ using fluorescence intensity ratio, which enables the monitorable photocatalysis. Furthermore, the nanoreactor with a multidimensional structure increases effective intermolecular collisions to facilitate the catalytic process by restricting the reaction within distinct enclosed spaces and circumvents potential unknown interaction effects. The design of multi-space nanoconfined reactors opens up a new avenue to modulate catalyst function, providing a unique perspective for photocatalytic applications in the mineralization of organic pollutants, hydrogen production, and nitrogen fixation.

17.
J Colloid Interface Sci ; 670: 297-310, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38763026

RESUMEN

Fenton/Fenton-like reaction induced chemical dynamic therapy (CDT) has been widely recognized in tumor therapy. Due to the low efficiency of conversion from high-valent metal ions (M(n+1)+) to low-valent ions (Mn+) in the Fenton/Fenton-like catalytic process, enhancing the conversion efficiency safely and effectively would create a great opportunity for the clinical application of CDT. In the study, a universal nanoreactor (NR) consisting of liposome (Lip), tumor cell membrane (CM), and bis(2,4,5-trichloro-6-carboxyphenyl) oxalate (CPPO) is developed to tackle this challenge. The CPPO was first discovered to decompose under weak acidity and H2O2 conditions to generate carboxylic acids (R'COOH) and alcohols (R'OH) with reducibility, which will reduce M(n+1)+ to Mn+ and magnify the effect of CDT. Furthermore, glucose oxidase (GOx) was introduced to decompose glucose in tumor and generate H2O2 and glucose acid, which promote the degradation of CPPO, further strengthening the efficiency of CDT, leading to a butterfly effect. This demonstrated that the butterfly effect triggered by NR and GOx encourages Fenton/Fenton-like reactions of Fe3O4 and MoS2, thereby enhancing the tumor inhibition effect. The strategy of combining GOx and CPPO to strengthen the Fenton/Fenton-like reaction is a universal strategy, which provides a new and interesting perspective for CPPO in the application of CDT, reflecting the exquisite integration of Fenton chemistry and catalytic medicine.


Asunto(s)
Peróxido de Hidrógeno , Peróxido de Hidrógeno/química , Humanos , Hierro/química , Liposomas/química , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Animales , Propiedades de Superficie , Antineoplásicos/química , Antineoplásicos/farmacología , Oxalatos/química , Ratones , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacos
18.
Acta Biomater ; 181: 402-414, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38734282

RESUMEN

Tumor hypoxia, high oxidative stress, and low immunogenic create a deep-rooted immunosuppressive microenvironment, posing a major challenge to the therapeutic efficiency of cancer immunotherapy for solid tumor. Herein, an intelligent nanoplatform responsive to the tumor microenvironment (TME) capable of hypoxia relief and immune stimulation has been engineered for efficient solid tumor immunotherapy. The MnO2@OxA@OMV nanoreactor, enclosing bacterial-derived outer membrane vesicles (OMVs)-wrapped MnO2 nanoenzyme and the immunogenic cell death inducer oxaliplatin (OxA), demonstrated intrinsic catalase-like activity within the TME, which effectively catalyzed the endogenous H2O2 into O2 to enable a prolonged oxygen supply, thereby alleviating the tumor's oxidative stress and hypoxic TME, and expediting OxA release. The combinational action of OxA-caused ICD effect and Mn2+ from nanoreactor enabled the motivation of the cGAS-STING pathway to significantly improve the activation of STING and dendritic cells (DCs) maturation, resulting in metalloimmunotherapy. Furthermore, the immunostimulant OMVs played a crucial role in promoting the infiltration of activated CD8+T cells into the solid tumor. Overall, the nanoreactor offers a robust platform for solid tumor treatment, highlighting the significant potential of combining relief from tumor hypoxia and immune stimulation for metalloimmunotherapy. STATEMENT OF SIGNIFICANCE: A tailor-made nanoreactor was fabricated by enclosing bacterial-derived outer membrane vesicles (OMVs) onto MnO2 nanoenzyme and loading with immunogenic cell death inducer oxaliplatin (OxA) for tumor metalloimmunotherapy. The nanoreactor possesses intrinsic catalase-like activity within the tumor microenvironment, which effectively enabled a prolonged oxygen supply by catalyzing the conversion of endogenous H2O2 into O2, thereby alleviating tumor hypoxia and expediting OxA release. Furthermore, the TME-responsive release of nutritional Mn2+ sensitized the cGAS-STING pathway and collaborated with OxA-induced immunogenic cell death (ICD). Combing with immunostimulatory OMVs enhances the uptake of nanoreactors by DCs and promotes the infiltration of activated CD8+T cells. This nanoreactor offers a robust platform for solid tumor treatment, highlighting the significant potential of combining relief from tumor hypoxia and immune stimulation for metalloimmunotherapy.


Asunto(s)
Inmunoterapia , Microambiente Tumoral , Animales , Inmunoterapia/métodos , Ratones , Microambiente Tumoral/efectos de los fármacos , Línea Celular Tumoral , Hipoxia Tumoral/efectos de los fármacos , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Oxaliplatino/farmacología , Oxaliplatino/química , Óxidos/química , Óxidos/farmacología , Manganeso/química , Manganeso/farmacología , Humanos , Femenino , Neoplasias/terapia , Neoplasias/patología , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Células Dendríticas/inmunología , Ratones Endogámicos C57BL
19.
J Colloid Interface Sci ; 669: 657-666, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38733877

RESUMEN

Creating a microenvironment for enhanced peroxymonosulfate (PMS) activation is vital in advanced oxidation processes. The objective of this study was to fabricate nanoshells composed of titanium dioxide embedded with cobalt titanate nanoparticles of perovskite to act as nanoreactors for effectively initiating PMS and degrading contaminants. The unique porous structure and confined space of the nanoreactor facilitated reactant absorption and mass transfer to the active sites, resulting in exceptional catalytic performance for pollutant elimination. Experimental findings revealed close to 100% decomposition efficiency of 4-chlorophenol (4-CP) within an hour utilizing the nanoreactors over a wide pH range. The TiO2/CoTiO3 hollow nanoshells catalysts also displayed adaptability in disintegrating organic dyes and antibiotics. The radicals SO4•-, •OH, and non-radicals 1O2 were determined to be accountable for eliminating pollutants, as supported by trapping experiments and electron paramagnetic resonance spectra. The catalyst was confirmed as an electron donor and PMS as an electron acceptor through electrochemical tests and density functional theory calculations. This study underscores the potential of incorporating stable perovskite catalysts in hollow nanoreactors to enhance wastewater treatment.

20.
J Colloid Interface Sci ; 669: 679-687, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38733879

RESUMEN

Nanoscale graphene-semiconductor composite photocatalysts with fascinating properties in the photocatalytic hydrogen evolution have inspired numerous interests in broad research fields. The architectures with efficient light response and promoting charge separation at the interface between reduced graphene oxide (RGO) and semiconductor are critical, yet synthesizing them remains a formidable challenge. Herein, the photodiode array-like LaNiO3/N,P-RGO (LNO/N,P-RGO) nanoreactor was constructed using an innovative strategy of acid etching-induced nanocutting self-assembly. Ammonium dihydrogen phosphate working as both a nitrogen phosphorus co-dopant and an acid etching reagent, cuts perovskite LaNiO3 (LNO) nanoparticles into nanorods, which are bonded evenly on the nitrogen phosphorus co-doped reduced graphene oxide (N,P-RGO) to form an n-n semiconductor heterojunction LNO/N,P-RGO as a photodiode array-like nanoreactor via hydrothermal treatment. The photodiode array-like nanostructure exposes more active sites that are conducive to light absorption. The robust Ni-C and P-O bonds promote the narrowing of space-charge region at the interface by UV irradiation, thereby improving the transport of photogenerated carriers by visible light irradiation. The LNO/N,P-RGO nanoreactor exhibits excellent photocatalytic hydrogen evolution performance with a yield of up to 354 µmol g-1 h-1 under UV-visible light, which is 50 times higher than that of pure perovskite LNO, and it also displays favorable recycling stability.

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