Enzyme‐Mediated In Situ Self‐Assembly AIE Probes: Mapping the Distribution of Acetylcholinesterase in Aging Mice Brain

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Acetylcholinesterase (AChE) exhibits profound association with the underlying pathological mechanisms of aging‐related disorders. However, revealing spatial distribution AChE among whole‐brain remains an uncharted territory, posing a substantial challenge. Herein, dual regulation strategy to obtain aggregation‐induced emission (AIE)‐activable probe for high‐fidility mapping in brain is proposed. The well‐tailored (AChE‐QM‐2) consists four components: AChE‐specific cleavage unit (dimethylcarbamate), self‐immolative linker ( p ‐hydroxybenzyl alcohol), AIE framework (Py‐QM), and electron‐donor group (EDG). hydrophilic pyridine salt AChE‐QM‐2 improves its dispersity, collaborating EDG lower Δ E S1‐T1 HOMO‐LUMO energy gap, resulting reduced fluorescence quantum yield Φ f ) initial off‐fluorescence state. Moreover, optimizing EDGs further enhance probe's responsive performance extend wavelength. Upon AChE‐activization, undergoes deionization, molecule aggregation increased , triggering amplified signal. has successfully realized monitoring endogenous PC12 cells, tissues living mice. Furthermore, utilizing light‐sheet microscopy, intracranial AChE, providing highly specialized visualization localization within brain, achieved first time. This study satisfactorily demonstrates valuable designing ultra‐sensitive enzymatic probes, highlighting their potential precise analysis fundamental life science research.

Language: Английский

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Atomic Engineering and Aggregation Effect to Regulate Synergistically Type I Reactive Oxygen Species of AIE‐Active Deep Red/Near Infrared Red Photosensitizer

Small, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract “Molecular science” has long been regarded as the golden rule to guide design of organic materials’ performances in past many years, but some interesting phenomena conventional aggregation‐caused fluorescence quenching and new aggregation‐induced emission reflect that properties would be changed from “molecule” “aggregate”. Therefore, “molecular theory faces certain limitations regulating performance materials at aggregation. In this work, it is discovered photosensitizer's contain reactive oxygen species, which could affected by changing molecular atoms aggregation form. The introduction selenium redshift improve species (ROS) efficiency. addition atomic effect, ROS efficiency photosensitizers after coating a polymeric shell, is, production type II singlet ( 1 O 2 ) suppressed, while I superoxide anion (O −• improved. This work discovers are relevant effect discussing deeply influence mechanism, important research significance for modulating precisely promoting development photodynamic therapy.

Language: Английский

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Biomaterials to regulate tumor extracellular matrix in immunotherapy

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 376, P. 149 - 166

Published: Oct. 11, 2024

Language: Английский

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Nanomaterial-based regulation of redox metabolism for enhancing cancer therapy

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

This review provides a comprehensive summary of the dysregulation redox metabolism in cancer cells and advantages latest advances nanomaterial-assisted metabolic regulation therapy.

Language: Английский

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Nitric Oxide-Producing Multiple Functional Nanoparticle Remodeling Tumor Microenvironment for Synergistic Photodynamic Immunotherapy against Hypoxic Tumor

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

The treatment of pancreatic cancer faces significant challenges due to connective tissue hyperplasia and severe hypoxia. Unlike oxygen-dependent Type II photosensitizers, I photosensitizers can produce a substantial amount reactive oxygen species, even under hypoxic conditions, making them more suitable for photodynamic therapy cancer. However, the dense extracellular matrix limits penetration efficiency presence immunosuppressive cells in tumor microenvironment reduces therapeutic effect. To address these challenges, we designed photoimmunotherapeutic M1@PAP nanoparticles composed photosensitizer anti-PD-L1 siRNA (siPD-L1), which was encapsulated into M1 macrophage membrane vesicles. In this system, pyropheophorbide-a (PPA) covalently conjugated poly-l-arginine (Arg9). Notably, it capable generating sufficient superoxide anions thereby functioning as photosensitizer. Furthermore, Arg9 acted nitric oxide (NO) donor, enhancing nanophotosensitizer by inhibiting cancer-associated fibroblast (CAF) activation decomposing matrix. Additionally, vesicles provided active targeting capabilities reeducated immunosuppressed M2 macrophages. reversal further promoted efficacy immunotherapy, showing great potential synergistic immunotherapy against tumor.

Language: Английский

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Direct and indirect approaches to red-shift photoactivated nitric oxide release

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 515, P. 215921 - 215921

Published: May 21, 2024

Nitric oxide (NO) is an important biochemical molecule that endogenously produced to act for instance as neurotransmitter, effect cell growth, or regulate the immune response. Therapeutic treatment with exogeneous NO difficult owing its gaseous and reactive nature and, not surprising, specific molecules deliver have been developed. Amongst various triggers deliberately release from these NO-releasing molecules, light most elegant allows a high degree of control over time location NO-release. For therapeutic applications, it necessary use long-wavelength light, preferably in red near infrared region, which challenging achieve. This review gives overview on approaches red-shift activation wavelength light-activated NO-release nitrosoamines, o-substituted nitroarenes, L-arginine, cupferron, nitrosyl metal complexes. While focusing single photon excitation events, direct mechanisms are covered well photoelectron transfer, energy chemiluminescence photothermal light-triggered oxidation pathways. each NO-releaser class, photochemical mechanism discussed, biological applications mentioned.

Language: Английский

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Gas immnuo-nanomedicines fight cancers

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117595 - 117595

Published: Oct. 31, 2024

Certain gas molecules, including hydrogen (H

Language: Английский

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Nitric Oxide‐Releasing Nanoscale Metal‐Organic Layer Overcomes Hypoxia and Reactive Oxygen Species Diffusion Barriers to Enhance Cancer Radiotherapy

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Abstract Hafnium (Hf)‐based nanoscale metal‐organic layers (MOLs) enhance radiotherapeutic effects of tissue‐penetrating X‐rays via a unique radiotherapy‐radiodynamic therapy (RT‐RDT) process through efficient generation hydroxy radical (RT) and singlet oxygen (RDT). However, their efficacy is limited by hypoxia in deep‐seated tumors short half‐lives reactive species (ROS). Herein the conjugation nitric oxide (NO) donor, S‐nitroso‐N‐acetyl‐DL‐penicillamine (SNAP), to Hf 12 secondary building units (SBUs) Hf‐5,5′‐di‐p‐benzoatoporphyrin MOL reported afford SNAP/MOL for enhanced cancer radiotherapy. Under X‐ray irradiation, efficiently generates superoxide anion (O 2 −. ) releases spatio‐temporally synchronized fashion. The released NO rapidly reacts with O form long‐lived highly cytotoxic peroxynitrite which diffuses freely cell nucleus causes DNA double‐strand breaks. Meanwhile, sustained release from tumor microenvironment relieves reduce radioresistance cells. Consequently, plus low‐dose irradiation inhibits growth reduces metastasis colorectal triple‐negative breast models.

Language: Английский

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Endoplasmic Reticulum Targeting Nanoparticle for Efficient Anti-Tumor Immunotherapy

ACS Applied Nano Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Despite significant clinical breakthroughs in anti-tumor immunotherapy, its therapy efficiency remains hindered by insufficient "cold" tumor immune responses. The ample reactive oxygen species photodynamic (PDT) can trigger the immunogenic cell death (ICD) pathway for arousing system and realizing immunotherapy. But inherent hypoxic microenvironment (TME) limits PDT efficacy. To simultaneously reverse TME promote ICD pathway, multi-in-one nanostructure (FAIC) is designed, which catalase (CAT) photosensitizer (I-Cy5) are encapsulated a folate receptor-targeting liposome. Due to endoplasmic reticulum (ER)-targeting ability of I-Cy5, H2O2 decomposition catalytic CAT, cell-targeting liposome, severe ER stress triggered nano FAIC pathway. As result, infiltration cytotoxic T lymphocytes promoted, response boosted. design corresponding mechanism provide potential way realize efficient

Language: Английский

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Harnessing stimuli-responsive NO nanomaterials for advanced multi-disease therapy

Coordination Chemistry Reviews, Journal Year: 2025, Volume and Issue: 533, P. 216540 - 216540

Published: Feb. 27, 2025

Language: Английский

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