Trilocked Photodynamic Senolytic Inducer Potentiating Immunogenic Senescent Cell Removal for Liver Fibrosis Resolution

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Апрель 30, 2025

Liver fibrosis is a major global health problem without effective therapies, and targeted elimination of senescent cells beneficial for hepatic function organism survival. We report new trilocked photodynamic senolytic inducer (PDSI) strategy liver resolution using type-I agent immunogenic clearance cells. demonstrate that this PDSI not only facilitates efficient production superoxide anions (O2•-) in lysosomes therapy, but also permits NIR fluorescence photoacoustic (NIRF/PA) imaging Mechanistic investigation reveals the elicited cell predominantly via necroptosis pathway. Moreover, with liver-targeting moiety enables high-contrast NIRF/PA vivo. This exhibits remarkable ablation cells, enhancing dendritic maturation cytotoxic T recruitment fibrosis. Our study highlights potential type I boosting immunity treatment.

Язык: Английский

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Polymer Conjugation Benefits Proteins Beyond Simply Extended Half-life

Acta Biomaterialia, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

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Single-Molecule Macrocyclic Carrier Overcomes the Direct Transmembrane of Medium-Sized Cargoes

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Июнь 3, 2025

Direct transmembrane transport plays an important role in the biomedical field. Although well-established methods exist for direct membrane of small-sized cargoes (e.g., water and ions) large-sized proteins, DNAs, polysaccharides), they are challenging to directly apply medium-sized drugs, probes, oligopeptides, growth hormones). Here, we present a negatively charged single molecular carrier, carboxyl-modified azocalix[6]arene (CAC6A), as tool that facilitates cargoes. The cellular uptake pathway CAC6A was identified using pharmacological inhibitors, confirmed. Further mechanistic investigations reveal modification group at upper rim, cavity size, appropriate amphiphilicity promote transport. Combined with hypoxia-responsive property, achieved targeted release payload. findings this work may lead development macrocycle-based systems broad applications biomedicine, diagnostics, sensing.

Язык: Английский

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PEGylation Can Effectively Strike a Balance in siRNA Delivery Performances of Guanidinylated Linear Synthetic Polypeptides with Potential Use for Transcriptional Gene Silencing

ACS Macro Letters, Год журнала: 2024, Номер unknown, С. 1251 - 1257

Опубликована: Сен. 11, 2024

The prevailing design philosophy for polymeric vectors delivering siRNA is rooted in the post-transcriptional gene silencing (PTGS) mechanism. Yet, transcriptional (TGS) mechanism offers a potentially more durable effect, which necessitates efficient delivery into nucleus. However, it remains challenge to efficiently deliver We have explored guanidinylated cyclic synthetic polypeptides (GCSPs) enhance nuclear of siRNA, but an increased cytotoxicity and difficulty producing GCSPs on large scale limit their utility. Herein, we simply prepare PEGylated linear (PGLSPs) exhibiting improved membrane penetration, direct transport nucleus, reduced toxicity, high cellular uptake, mitigation protein corona formation. PEGylation can effectively balance vector's capacity with other critical aspects performances delivery. Therefore, PGLSPs hold promise as TGS-based vectors, offering potential future therapeutic applications.

Язык: Английский

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Glycosylated AIE‐active Red Light‐triggered Photocage with Precisely Tumor Targeting Capability for Synergistic Type I Photodynamic Therapy and CPT Chemotherapy

Angewandte Chemie International Edition, Год журнала: 2024, Номер 64(1)

Опубликована: Сен. 13, 2024

Photocaging is an emerging protocol for precisely manipulating spatial and temporal behaviors over biological activity. However, the red/near-infrared light-triggered photolysis process of current photocage largely singlet oxygen (

Язык: Английский

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Mechanistic Insights into the Tools for Intracellular Protein Delivery

Chem & Bio Engineering, Год журнала: 2024, Номер 2(3), С. 132 - 155

Опубликована: Дек. 23, 2024

Proteins are an important therapeutic modality in modern medicine. However, their inherent inability to traverse cell membranes essentially limits application extracellular targets. Recent advances intracellular protein delivery have enabled access traditionally "undruggable" targets and paved the way precisely modulate cellular functions. This Review provides a comprehensive examination of key mechanisms emerging technologies that facilitate transport functional proteins across membranes. Delivery methods categorized into physical, chemical, biological approaches, each with distinct advantages limitations. Physical enable direct entry but often pose challenges related invasiveness technical complexity. Chemical strategies offer customizable solutions enhanced control over targeting uptake, yet may face issues cytotoxicity scalability. Biological approaches leverage naturally occurring processes achieve efficient transport, though regulatory production consistency remain hurdles. By highlighting recent advancements, challenges, opportunities within approach, this review underscores potential unlock new pathways transform drug development paradigms.

Язык: Английский

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Glycosylated AIE‐active Red Light‐triggered Photocage with Precisely Tumor Targeting Capability for Synergistic Type I Photodynamic Therapy and CPT Chemotherapy

Angewandte Chemie, Год журнала: 2024, Номер 137(1)

Опубликована: Сен. 13, 2024

Abstract Photocaging is an emerging protocol for precisely manipulating spatial and temporal behaviors over biological activity. However, the red/near‐infrared light‐triggered photolysis process of current photocage largely singlet oxygen ( 1 O 2 )‐dependent lack compatibility with other reactive species (ROS)‐activated techniques, which has proven to be major bottleneck in achieving efficient precise treatment. Herein, we reported a lactosylated BT‐LRC by covalently incorporating camptothecin (CPT) into hybrid BODIPY‐TPE fluorophore via superoxide anion radical (O − ⋅)‐cleavable thioketal bond type I photodynamic therapy (PDT) anticancer drug release. Amphiphilic could self‐assembled aggregation‐induced emission (AIE)‐active nanoparticles (BT‐LRCs) owing regulation carbohydrate‐carbohydrate interactions (CCIs) among neighboring lactose units nanoaggregates. BT‐LRCs simultaneously generate abundant ⋅ through aggregation modulated interactions, DNA‐damaging agent CPT was subsequently effectively released. Notably, PDT chemotherapy collaboratively amplified therapeutic efficacy HepG2 cells tumor‐bearing mice. Furthermore, inherent AIE property endowed photocaged prodrug superior bioimaging capability, provided powerful tool real‐time tracking finely tuning photoactivated release behavior tumor therapy.

Язык: Английский

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Glycosylated AIE-active Fe (III) photosensitizer activated by tumor microenvironment for synergistic type I photodynamic and chemodynamic therapy

Nanoscale, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

This work presents a novel tumor microenvironment-activated photosensitizer employed for the combined action of photodynamic therapy (PDT) and chemodynamic (CDT), which synergistically functions to effectively kill cells.

Язык: Английский

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