Aggregate (Hoboken, N.J.)最新文献

The rise in pancreatic diseases, resulting from improved living quality and lifestyle habits changes, has imposed a serious social burden. To better understand the pancreatic functions during disease progression, constructing a bionic pancreas is vital yet challenging in tissue engineering. Herein, inspired by the physiological anatomy of the pancreas, we introduce core-shell microfibers with pancreatic stellate cells (PSCs) in the shell and pancreatic β-cells in the core. Compared to traditional plate culture, the β-cells encapsulated in the microfiber exhibit enhanced glucose-stimulated insulin secretion. Such microfibers also serve as a platform to study the progression of diabetes of the exocrine pancreas, where the PSCs are activated under conditions of pancreatic exocrine diseases such as chronic pancreatitis. The activated PSCs impede insulin synthesis and increase apoptosis in β-cells, resulting in elevated blood glucose. This high-glucose microenvironment further exacerbates the activation of PSCs, causing a vicious cycle of diabetes. Additionally, the bio-inspired pancreas also demonstrates its potential in drug screening, as evidenced by testing the glucagon-like peptide 1 receptor agonist, Exendin-4. Building upon such features, it is convincing that these multi-component microfibers hold promise for exploring the pancreatic exocrine and endocrine interactions, and showing potential in disease modeling, drug screening, and regenerative medicine.

Immunotherapy has emerged as one of the most promising strategies for achieving complete tumor eradication. However, its effectiveness against solid tumors remains limited due to the presence of an immunosuppressive tumor microenvironment. In addition, severe side effects such as cytokine storms further constrain its clinical application. Therefore, there is an urgent need to develop efficient and controllable immunotherapeutic approaches. Herein, we report the development of a novel mitochondrial DNA-releasing photosensitizer, MQ-PPy, which exhibits outstanding mitochondrial localization and robust reactive oxygen species generation. Upon light irradiation, MQ-PPy induces pronounced mitochondrial oxidative damage in tumor cells, triggering the release of immunogenic damage-associated molecular patterns and mitochondrial DNA, which activates the cGAS-STING signaling pathway. Meanwhile, MQ-PPy effectively induces immunogenic cell death, thereby remodeling the tumor immune microenvironment and enhancing antitumor immune responses. In vivo studies confirmed that MQ-PPy-mediated photodynamic therapy significantly inhibits tumor growth and notably increases the infiltration of cytotoxic T cells within the tumor. Moreover, we demonstrated that tumor cells treated with MQ-PPy-mediated PDT can function as a whole-cell vaccine, effectively establishing systemic immune memory and significantly suppressing tumor growth upon rechallenge. This study presents a promising and controllable strategy for advancing tumor immunotherapy through mitochondria-targeted photoactivation.

Mitochondria-targeted aggregation-induced emission (AIE) materials have emerged as promising candidates for precision medicine by enabling the controllable induction of oxidative stress within mitochondria. Yet, a comprehensive overview of the antitumor and other biological effects resulting from such oxidative stress remains lacking. This review summarizes the roles of both excessive and moderate oxidative stress triggered by mitochondria-targeted AIE materials across diverse applications, including: (1) direct induction of various forms of cancer cell death and degradation of cancer-associated proteins; (2) synergistic enhancement of chemo-, radio-, immune-, and other therapies; and (3) treatments beyond cancer. In addition, the challenges and key issues limiting their broader application are discussed. This review highlights the therapeutic potential of controllably induced oxidative stress by mitochondria-targeted AIE materials, aiming to accelerate their development for precise disease intervention and biological regulation.

Gliomas present a significant challenge in oncology due to their often subtle early symptoms and the insidious nature of their growth, which is compounded by the blood–brain barrier. Recent evidence has highlighted the diagnostic and therapeutic potential of monocytes, macrophages, and microglia in the context of glioma. This review focused on emerging evidence and hypotheses concerning the components and interrelationships within the mononuclear phagocyte system (MPS) in the central nervous system and its role in glioma development and invasion. By summarizing the involvement of the MPS in glioma biology, this paper offers a novel perspective for the integration of liquid biopsy and targeted therapies in oncology.

Apoptotic vesicles (ApoVs) are membrane structures formed during cell apoptosis and play crucial roles in homeostasis maintenance, signal transduction, and immune regulation. Importantly, ApoVs inherit the properties and contents of parental cells that show great potential in the diagnosis and treatment of diseases. Monitoring the formation process of ApoVs (such as quantity, morphological changes, release rules, etc.) can reveal the regulatory mechanism of apoptosis, and is also helpful for optimizing the preparation and application of ApoVs. However, due to the limitations of existing technologies, the formation processes of ApoVs have been challenging to precisely and entirely capture. Herein, we subtly constructed a versatile AIEgen (ADTP) that could induce ApoVs production and in situ monitor the formation process, and it was successfully applied to explore the formation mechanism of ApoVs. ADTP specifically targeted the plasma membrane, and it could effectively induce apoptosis under laser irradiation, so it was able to dynamically monitor the entire formation process of ApoVs and had validated ApoVs formation from membrane protrusions (including filopodia, tunneling nanotubes, and retraction fibers). Further investigation revealed that ApoVs derived from membrane protrusions with different components exhibited significant heterogeneity. Additionally, the near-infrared emission characteristic of ADTP was compatible with the stimulated emission depletion (STED) microscopy equipped with a 775 nm depletion laser, enabling high-resolution visualization of detailed dynamic changes in membrane protrusions during ApoVs formation. This work provided powerful tools for tracking the entire ApoVs formation process and also offered crucial scientific evidence for revealing the ApoVs formation mechanism.

Stacking angles played a decisive role in the coupling strength of the excited state, the overlap of electronic orbitals, and behavior of excitons, which further have ultimately affected the luminescent properties. However, developing effective strategies to precisely tailor molecular stacking anglets of chromophores still remains challenges. In this work, we constructed a series of figure-eight supramolecules S1–S3 through the coordination-driven self-assembly of anthracene-based 180° di-platinum(II) acceptor L and ditopic pyridyl ligands L1–L3, respectively. Variation in ligand length enabled regulation of intramolecular anthracene stacking angles in the assembled structures and photoluminescent properties. Photophysical studies revealed that larger stacking angles significantly enhance fluorescent intensities and photoluminescence quantum yields in both solution and solid states. Femtosecond transient absorption spectroscopy further demonstrated that the excited-state lifetimes of S1–S3 were extended due to suppressed non-radiative decay pathways. Moreover, density functional theory calculations showed that the increasing stacking angles weakened intramolecular anthracene interactions, leading to enhanced radiative transition rates. This study elucidated the relationship of molecular packing and luminescent properties, which will pave the way for construction of materials with excellent luminescent performance.

The rational design of aqueous-phase supramolecular catalysts that integrate substrate recognition, activation, reaction selectivity, and recyclability remains a significant challenge. This work presents a cucurbit[8]uril (Q[8])-based supramolecular photocatalyst, TMV⁸⁺@Q[8], which selectively encapsulates aromatic sulfide substrates via host-stabilized charge transfer (HSCT) interactions while markedly enhancing singlet oxygen (¹O₂) generation. Under visible-light irradiation, the substrate-TMV⁸⁺@Q[8] system facilitates the efficient catalytic oxidation of aromatic sulfides to sulfoxides. Competitive displacement experiments confirm that product desorption is substrate-driven, enabling catalyst regeneration. Crucially, the Q[8] cavity plays a multifaceted role by enhancing substrate activation through HSCT, promoting ¹O₂-mediated oxidation via confinement effects, and enforcing selectivity through size exclusion. These findings establish a new paradigm for supramolecular photocatalysis, wherein macrocyclic confinement concurrently enhances substrate recognition, catalytic efficiency, and recyclability. This study thereby provides a strategic blueprint for designing enzyme-inspired supramolecular photocatalysts operable in aqueous media.

The management of iodine species, notorious for their environmental persistence and health risks, requires innovative materials capable of efficient capture and conversion. Herein, we report the self-assembly and characterization of a Zr-based metal–organic tetrahedron (1) functionalized with redox-active triazatriangulenium (TATA⁺) panels. The cage exhibits a high binding affinity for triiodide (I₃⁻) (ca. 10⁶ M⁻¹) in methanol. The strong host–guest complexation significantly facilitates the disproportionation hydrolysis of I₂ to generate I₃⁻ and HOI. It also enables photocatalytic aerobic oxidation of I⁻ into I₃⁻ within its cavity. Mechanistic investigations revealed the key steps involving guest-to-host photoinduced electron transfer (ET) to generate radicals I^• and 1^• and ET from 1^• to dioxygen to generate superoxide. Solid-state adsorption experiments showed the rapid removal of I₂ and I₃⁻ from water by 1-NTf₂ because of the high affinity for polyiodides. Importantly, although solid-state 1-NTf₂ has no ability to directly adsorb I⁻ from water, we have for the first time developed a light-driven strategy that enables removal of I⁻ through coupled photooxidation and sequestration. This work highlights the significant potential of integrating photoredox-active moieties within stable metal–organic cages for controlling iodine binding and speciation and opens new avenues to address environmental and energy-related sequestration challenges.

Organic photothermal materials based on conjugated structures hold great potential for solar harvesting but are often constrained by narrow absorption and limited solar–thermal conversion efficiency. A general molecular design strategy that can simultaneously broaden absorption and enhance nonradiative decay remains elusive. Here, we pioneer a quinoid–donor–acceptor (Q–D–A) architecture specifically tailored for photothermal applications. Incorporating quinoidal unit into a D–A polymer backbone yields the novel polymer PAQM-TBz, which exhibits a reinforced backbone planarity, intensified π–π interactions, and enhanced diradical character compared with its D–A analogue, P2T-TBz. These synergistic features enable broadband absorption (400–1500 nm) and rapid nonradiative relaxation, yielding an outstanding photothermal conversion efficiency of 80.6% under 808 nm laser irradiation—nearly twice that of P2T-TBz. Under 1.0 kW m^‒2 simulated sunlight, PAQM-TBz achieves a record-high solar-to-vapor efficiency of 97.3% with an evaporation rate of 1.41 kg m^‒2 h^‒1. It also generates a peak thermoelectric voltage of 126.1 mV, and in integrated water–electricity cogeneration, attains an evaporation rate of 1.28 kg m^‒2 h^‒1 and a voltage 95.8 mV, ranking among the highest for organic materials. This work establishes the Q–D–A strategy as a transformative platform for advanced solar–thermal energy conversion and multifunctional solar-harvesting applications.

Supramolecular assembly is a versatile bottom-up strategy for creating advanced functional materials. Metallic platinum–platinum (Pt···Pt) interactions provide a distinctive driving force for supramolecular assembly due to their strong, directional, and long-range nature. Despite their importance, the microscopic dynamics underlying the self-assembly of Pt(II) complexes remain challenging to probe experimentally. Molecular dynamics (MD) simulations can capture these processes at atomic resolution, but extracting kinetic pathways is complicated by the indistinguishability and permutation of identical monomers within self-assembled structures. In this study, we employ GraphVAMPnet, a deep learning framework based on graph neural networks (GNN), on extensive MD simulations of amphiphilic PtB complexes during the early stage of self-assembly. GraphVAMPnet inherently accounts for permutational, rotational, and translational invariance, making it well-suited for analyzing self-assembly dynamics. Our analysis reveals three slow collective variables (CVs) that govern PtB self-assembly. The slowest mode (CV1) separates two distinct kinetic growth routes: an incremental growth mechanism, in which single monomers join existing aggregates with predominantly antiparallel packing between two adjacent PtB complexes (CV3), and a hopping growth mechanism, in which clusters of smaller size merge via heterogeneous collisions, yielding a mix of antiparallel and parallel packing arrangements (CV2). Further energetic analysis indicates that incremental growth is favored, potentially leading to the well-ordered nanosheet morphologies observed experimentally. Our findings provide molecular-level insight into PtB self-assembly pathways and showcase the capability of GraphVAMPnet in dissecting the complex dynamics of supramolecular assembly.