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Indoleamine-2,3-dioxygenase-1 (IDO1) pathogenically suppresses immune cell infiltration and promotes tumor cell immune escape by overmetabolizing tryptophan to N-formyl kynurenine in the tumor microenvironment (TME). However, it remains challenging for IDO1 immune checkpoint inhibitors to achieve a significant potency of progression-free survival. Here, we developed a breakthrough in IDO1 inhibition by sono-targeted biobromination reaction using immunostimulating hypobromic-P-phenylperoxydibenzoic acid-linked metallic organic framework nanomedicine (H-MOF NM) to remodel the TME from debrominated hypoxia into hypobromated normoxia and activate the IDO1 immune pathway with in vitro and in vivo remarkable antitumor efficacy. H-MOF NM contains Br+ and O- active ingredients with an enlarged band gap to deactivate IDO1 through an innovative biochemical mechanism, taking control over brominating IDO1 amino acid residues at the active sites in the remodeled TME and subsequently activating the immune response, including DC maturation, T-cell activation, and macrophage polarization. Importantly, the H-MOF NM achieves multiple immune responses with high tumor regression potency by combination sono-immunotherapy. This study describes an excellent IDO1 inhibition strategy through the development of immune biobrominative H-MOF nanomedicine and highlights efficient combination immunotherapy for tumor treatment.
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Metal-halide perovskite (MHP) single crystals are emerging as potential competitors to their polycrystalline thin-film counterparts. These materials have shown the specific feature of extended absorbance towards the near-infrared (NIR) region, which promises further extension of their applications in the field of photovoltaics and photodetectors. This notable expansion of absorbance has been explained by the narrower effective optical bandgap of MHP single crystals promoted by their large thickness over several micrometres to millimetres. Herein, the attributes of the material's thickness and the measurement technique used to estimate these characteristics are discussed to elucidate the actual origins of the extended absorbance of MHP single crystals. Contrary to the general belief of the narrower bandgap of the MHP single crystals, we demonstrate that the extended NIR absorption in the MHP single crystals mainly originates from the combination of unique below-bandgap absorption of MHPs, the thickness of single crystals, and the technical limitation of the spectrophotometer, with the key attributes of (i) significantly large thickness of the MHP single crystals by suppressing the transmitted light and (ii) the detector's limited dynamic range. Combining the theoretical and experimental characterizations, we clarify the significant role of the large thickness together with the limited sensitivity of the detector in promoting the well-known red shift of the absorption onset of the MHP single crystals. The observations evidently show that in some special circumstances, the acquired absorption spectrum cannot reliably represent the optical bandgap of MHP materials. This highlights some misinterpretations in the estimation of the narrower optical bandgap of the MHP single crystals from conventional optical methods, while the optical bandgap is an inherent property independent of the thickness. The proposed broad applications of the MHP single crystals are dictated by their fascinating properties, and therefore, a deep insight into these features should be considered besides device applications, because much of their property-function relationships are still ambiguous and a subject of debate.
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The thioredoxin system is involved in cancer development and therefore is a promising target for cancer chemotherapy. Thioredoxin reductase (TrxR) is a key component of the thioredoxin (Trx) system, and is overexpressed in many cancers to inhibit apoptosis-related proteins. Alternatively, inhibition of thioredoxin reductase and upregulation of apoptosis factors provide a therapeutic strategy for anti-tumor treatment. In this study, an ultrasound-activatable meso-organosilica nanomedicine was prepared by integrating chloroquine (CQ) into hollow mesoporous organosilica (CQ@MOS). The meso-organosilica nanomedicine can inhibit the activity of thioredoxin reductase, elevate cellular reactive oxygen species (ROS) levels, upregulate the pro-apoptotic factors in the c-Jun N-terminal kinase (JNK) apoptosis pathway and induce autophagy inhibition, further resulting in mitochondrial membrane potential (MMP) depolarization and cellular ATP content decrease, ultimately causing significant damage to tumor cells. Moreover, CQ@MOS can efficiently deliver chloroquine into cancer cells and promote an enhanced sonodynamic effect for effective anti-tumor chemotherapy and sonodynamic therapy. This study may enlighten us on a new anti-tumor strategy and suggest its promising applications in cancer treatments.
Assuntos
Antineoplásicos , Apoptose , Nanomedicina , Tiorredoxina Dissulfeto Redutase , Humanos , Apoptose/efeitos dos fármacos , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Tiorredoxina Dissulfeto Redutase/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Regulação para Cima/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Cloroquina/farmacologia , Cloroquina/química , Compostos de Organossilício/química , Compostos de Organossilício/farmacologia , Animais , Linhagem Celular Tumoral , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Terapia por UltrassomRESUMO
Sonography with its non-invasive and deep tissue-penetrating characteristics, not only contributes to promising developments in clinical disease diagnosis but also obtains acknowledgments as a prospective therapeutic approach in the field of tumor treatment. However, it remains a challenge for sonography simultaneously to achieve efficient imaging and therapeutic functionality. Here, we present an innovative integrated diagnosis and treatment paradigm by developing the nanomedicine of percarbamide-bromide-mesoporous organosilica spheres (MOS) with RGD peptide modification (PBMR) by loading percarbamide and bromide in MOS which were prepared by a one-step O/W microemulsion method. The PBMR nanomedicine effectively modifies the tumor acoustic environment to improve sonoimaging efficacy and induces sonochemical reactions to enhance the production of reactive oxygen species (ROS) for tumor treatment efficiency under sonography. The combination of PBMR nanomedicine and SDT achieved multiple ROS generation through the controlled sonochemical reactions and significantly boosted the potency of sonodynamic therapy and induced significant tumor regression with non-invasive tissue penetrability and minimizing damage to healthy tissues. Simultaneously, the generation of oxygen gas in the sonochemical process augments ultrasound reflection, resulting in a 4.9-fold increase in imaging grayscale. Our research establishes an effective platform for the synergistic integration of sonoimaging and sonodynamic antitumor therapy, offering a novel approach for precise antitumor treatment in the potential clinical applications.
Assuntos
Nanomedicina , Compostos de Organossilício , Espécies Reativas de Oxigênio , Terapia por Ultrassom , Animais , Terapia por Ultrassom/métodos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Compostos de Organossilício/química , Camundongos Endogâmicos BALB C , Neoplasias/terapia , Neoplasias/diagnóstico por imagem , Oligopeptídeos/química , Linhagem Celular Tumoral , Camundongos Nus , Ultrassonografia/métodos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , FemininoRESUMO
The photoelectric characteristics of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) films significantly affect the power conversion efficiency and stability of Si/PEDOT:PSS hybrid solar cells. In this paper, we investigated PEDOT:PSS modification with alcohol ether solvents (dipropylene glycol methyl ether (DPM) and propylene glycol phenyl ether (PPH)). The reduction of PSS content and the transformation of the PEDOT chain from benzene to a quinone structure in PEDOT:PSS induced by doping with DPM or PPH are the reasons for the improved conductivity of PEDOT:PSS films. DPM and PPH doping improves the quality of silicon with the PEDOT:PSS heterojunction and silicon surface passivation, thereby reducing the surface recombination of charge carriers, which improves the photovoltaic performance of Si/PEDOT:PSS solar cells. Comparing the power conversion performance (PCE) and air stability of Si/PEDOT:PSS solar cells with DPM (13.24%), DPH (13.51%), ethylene glycol (EG, 13.07%), and dimethyl sulfoxide (DMSO, 12.62%), it is suggested that doping with DPM and DPH can replace DMSO and EG to enhance the performance of Si/PEDOT:PSS solar cells. The EG and DMSO solvents not only have a certain toxicity to the human body but also are not environmentally friendly. In comparison to DMSO and EG, DPM and DPH are more economical and environmentally friendly, helping to reduce the manufacturing cost of Si/PEDOT:PSS solar cells and making them more conducive to their commercial applications.
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Neuromorphic visual sensors (NVS) based on photonic synapses hold a significant promise to emulate the human visual system. However, current photonic synapses rely on exquisite engineering of the complex heterogeneous interface to realize learning and memory functions, resulting in high fabrication cost, reduced reliability, high energy consumption and uncompact architecture, severely limiting the up-scaled manufacture, and on-chip integration. Here a photo-memory fundamental based on ion-exciton coupling is innovated to simplify synaptic structure and minimize energy consumption. Due to the intrinsic organic/inorganic interface within the crystal, the photodetector based on monolithic 2D perovskite exhibits a persistent photocurrent lasting about 90 s, enabling versatile synaptic functions. The electrical power consumption per synaptic event is estimated to be≈1.45 × 10-16 J, one order of magnitude lower than that in a natural biological system. Proof-of-concept image preprocessing using the neuromorphic vision sensors enabled by photonic synapse demonstrates 4 times enhancement of classification accuracy. Furthermore, getting rid of the artificial neural network, an expectation-based thresholding model is put forward to mimic the human visual system for facial recognition. This conceptual device unveils a new mechanism to simplify synaptic structure, promising the transformation of the NVS and fostering the emergence of next generation neural networks.
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Compostos de Cálcio , Redes Neurais de Computação , Óxidos , Sinapses , Titânio , Óxidos/química , Titânio/química , Sinapses/fisiologia , Compostos de Cálcio/química , Humanos , Fótons , Visão Ocular/fisiologiaRESUMO
The dynamic defect tolerance under light soaking is a crucial aspect of halide perovskites. However, the underlying physics of light soaking remains elusive and is subject to debate, exhibiting both positive and negative effects. In this investigation, we demonstrated that surface defects in perovskite films significantly impact the performance and stability of perovskite solar cells, closely correlated with light soaking behaviors. Removing the top surface layer through adhesive tape, the surface defect density noticeably decreases, leading to enhanced photoluminescence (PL) efficiency, prolonged carrier lifetime, and higher conductivity. Consequently, the power conversion efficiency (PCE) of solar cells improves from 17.70% to 20.5%. Furthermore, we confirmed a positive correlation between surface defects and the light soaking effect. Perovskite films with low surface defects surprisingly exhibit a 3-fold increase in PL intensity and an 85% increase in carrier lifetime under 500 s of continuous illumination at an intensity of 100 mW/cm2. Beyond the conventional strategy of suppressing defect trapping, we propose increasing the capability of dynamic defect tolerance as an effective strategy to enhance the optoelectronic properties and performance of perovskite solar cells.