siRNA-Encapsulated Biomimetic Liposomes Effectively Inhibit Tumor Cells’ Hexosamine Biosynthesis Pathway for Attenuating Hyaluronan Barriers to Pancreatic Cancer Chemotherapy

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Pancreatic ductal adenocarcinoma (PDAC) poses significant therapeutic challenges due to excessive hyaluronic acid (HA) accumulation, which impedes drug delivery. Here, we present a targeted approach reduce HA production by specifically silencing glutamine-fructose-6-phosphate aminotransferase 1 (GFAT1), key enzyme of the hexosamine biosynthesis pathway (HBP) in pancreatic cancer cells. An engineered liposomal system for siGFAT1 delivery, PMLip@siGFAT1, characterized macrophage membrane camouflage, LFC131 peptide-mediated targeting, and calcium phosphate (CaP) as core, was designed ensure prolonged circulation, enhanced inflamed vascular endothelial penetration, subsequent effective tumor cell uptake endosomal escape. Consequently, PMLip@siGFAT1 markedly downregulated level PDAC microenvironment, decompressing vasculature weakening stromal barrier, turn improved permeability chemotherapeutics. In combination with Doxil, demonstrated potent antitumor efficacy minimal systemic toxicity. Importantly, unlike PEGPH20 (hyaluronidase), reduced invasiveness, while preserving skeletal muscle integrity. These findings highlight that holds great potential revitalize downregulation strategies delivery efficacy.

Язык: Английский

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Nanomaterial-based regulation of redox metabolism for enhancing cancer therapy

Chemical Society Reviews, Год журнала: 2024, Номер unknown

Опубликована: Янв. 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.

Язык: Английский

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Role of Ubiquitination-driven Metabolisms in Oncogenesis and Cancer Therapy

Seminars in Cancer Biology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets

Molecular Biomedicine, Год журнала: 2025, Номер 6(1)

Опубликована: Фев. 25, 2025

Abstract Pyroptosis is a regulated form of inflammatory cell death in which Gasdermin D (GSDMD) plays central role as the key effector molecule. GSDMD-mediated pyroptosis characterized by complex biological features and considerable heterogeneity its expression, mechanisms, functional outcomes across various tissues, types, pathological microenvironments. This particularly pronounced inflammation-related diseases tumors. In context diseases, GSDMD expression typically upregulated, activation macrophages, neutrophils, T cells, epithelial mitochondria triggers both pyroptotic non-pyroptotic pathways, leading to release pro-inflammatory cytokines exacerbation tissue damage. However, under certain conditions, may also serve protective immune function. The tumors more manner, where it can either promote evasion or, some instances, induce tumor death. As our understanding GSDMD's continues progress, there have been advancements development inhibitors targeting pyroptosis; however, these therapeutic interventions remain preclinical phase. review systematically examines cellular molecular complexities pyroptosis, with particular emphasis on roles cancer. Furthermore, underscores substantial potential target for precision medicine, highlighting promising clinical applications.

Язык: Английский

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Overcoming Tumor Hypoxic Bismuth-based Ternary Heterojunctions Enable Defect Modulation-augmented Tumor Sonocatalytic Immunotherapy

Biomaterials, Год журнала: 2024, Номер 315, С. 122962 - 122962

Опубликована: Ноя. 12, 2024

Язык: Английский

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“Internal Trouble and Outside Aggression” Strategy: Energy Deprivation Synergized With cGAS‐STING Pathway Activation for Stimuli‐Responsive Photodynamic‐Metal‐Metabolic Immunotherapy

Advanced Functional Materials, Год журнала: 2024, Номер unknown

Опубликована: Сен. 18, 2024

Abstract The aberrant metabolic activities of tumor cells not only facilitate proliferation but also impair immune cell function and cause an immunosuppressive microenvironment (TME). Thus, reshaping the TME while activating innate immunity is highly desirable challenging. Herein, a multifunctional immunomodulator engineered for near‐infrared light (NIR)‐triggered photodynamic‐metal‐metabolic immunotherapy via “internal trouble outside aggression” strategy. Specifically, endogenous exogenous stimuli‐responsive nanoagent prepared consisting photosensitizer chlorin e6 (Ce6) modified dense silica‐coated rare earth‐doped nanoparticles (ReNPs@SiO 2 (Ce6)), with in situ grown ZIF‐8 on surface loading glucose transporter‐1 (GLUT‐1) inhibitor Fasentin glutaminase‐1 bis‐2‐(5‐phenylacetamido‐1,3,4‐thiadiazol‐2‐yl)ethyl sulfide (BPTES). as‐obtained final product denoted as ReSZ(FB). ReSZ(FB) induces‐ mitochondrial damage releases DNA (mtDNA) NIR‐mediated PDT. Subsequently, Zn 2+ from collaborates mtDNA to activate cGAS‐STING pathway, initiating robust tumor‐specific response. Concurrently, BPTES triggeres energy deprivation by blocking uptake inhibiting glutamine decomposition, thereby reprogramming TME, alleviating immunosuppression. Tumor are damaged trapped into trouble” combining PDT deprivation, sharply enhanced lethality exposes cancer “outside aggression”. Overall, this provides promising paradigm therapy.

Язык: Английский

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Extracellular barrier via in situ cross-linked catechol for blocking tumor mass transport and synergistic chemotherapy

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 159880 - 159880

Опубликована: Янв. 1, 2025

Язык: Английский

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Anti‐Tumor Strategies Targeting Nutritional Deprivation: Challenges and Opportunities

Advanced Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 2, 2025

Higher and richer nutrient requirements are typical features that distinguish tumor cells from AU: cells, ensuring adequate substrates energy sources for cell proliferation migration. Therefore, deprivation strategies based on targeted technologies can induce impaired viability in which more sensitive than normal cells. In this review, nutrients required by related metabolic pathways introduced, anti-tumor developed to target described. addition the nutritional characteristics of other microenvironment (including macrophages, neutrophils, natural killer T cancer-associated fibroblasts) new also summarized. conclusion, recent advances targeting blockade reviewed, challenges prospects these discussed, theoretical significance optimizing clinical application nutrition strategies.

Язык: Английский

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A photo-accelerated nanoplatform for image-guided synergistic chemo-photodynamic therapy

Chinese Chemical Letters, Год журнала: 2025, Номер unknown, С. 110942 - 110942

Опубликована: Фев. 1, 2025

Язык: Английский

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Switchable Nanophotosensitizers as Pyroptosis Inducers for Targeted Boosting of Antitumor Photoimmunotherapy

Biomacromolecules, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Photodynamic therapy (PDT) has emerged as a promising modality for cancer treatment, but its clinical application is constrained by unexpected phototoxicity arising from nonspecific photosensitizer activation and their "always-on" nature. Herein, we developed switchable nanophotosensitizer, poly(cation-π) nanoparticles (NP), which achieves supramolecular assembly through cation-π interactions. By coupling choline cationic moieties with aromatic photosensitizers (ZnPc), the polymer facilitates self-assembly driven interactions NP engineering. Surprisingly, photoactivity of ZnPc was completely quenched upon complexation via interactions, thereby significantly avoiding skin phototoxicity. Upon targeting tumor cells, undergoes GSH-responsive degradation process that weakens leading to spontaneous restoration amplifying immunogenic pyroptosis. In vivo studies demonstrated achieved high inhibition rate 84% while effectively This work provides novel perspective enhancing safety efficacy PDT-based treatment.

Язык: Английский

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