Multifunctional Copper‐Phenolic Nanopills Achieve Comprehensive Polyamines Depletion to Provoke Enhanced Pyroptosis and Cuproptosis for Cancer Immunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(45)

Опубликована: Сен. 17, 2024

Abstract The overexpression of polyamines in tumor cells contributes to the establishment immunosuppressive microenvironment and facilitates growth. Here, it have ingeniously designed multifunctional copper‐piceatannol/HA nanopills (Cu‐Pic/HA NPs) that effectively cause total intracellular depletion by inhibiting synthesis, depleting polyamines, impairing uptake, resulting enhanced pyroptosis cuproptosis, thus activating a powerful immune response achieve anti‐tumor therapy. Mitochondrial dysfunction from overall not only leads surge copper ions mitochondria, thereby causing aggregation toxic proteins induce but also triggers accumulation reactive oxygen species (ROS) within which further upregulates expression zDHHC5 zDHHC9 promote palmitoylation gasdermin D (GSDMD) GSDMD‐N, ultimately inducing pyroptosis. Then occurrence cuproptosis is conductive remodel microenvironment, responses growth metastasis. This therapeutic strategy through comprehensive provides novel template for cancer immunotherapy.

Язык: Английский

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Dual Metal Nanoflower Oxygen Pump Microneedles Based on Cuproptosis and STING Pathway Activation for Cancer Immunotherapy

Small, Год журнала: 2025, Номер 21(11)

Опубликована: Фев. 14, 2025

Abstract Immunotherapy is a promising new approach for tumor treatment. However, its clinical application hindered by insufficient immunogenicity, hypoxia, and immunosuppressive microenvironment (TME). Here, oxygen pump microneedles (OPMNs) loaded with zinc‐doped copper sulfide nanoflowers (ZCS NFs) PD‐L1 small interfering RNA (siPD‐L1) (OPMNs‐ZCS@siPD‐L1) are developed boosting immunotherapy. OPMN‐ZCS@siPD‐L1 enhances immunogenicity through ZCS NFs inducing cuproptosis, reverses TME siPD‐L1, promotes drug penetration, ameliorates hypoxia bubbles. More importantly, cuproptosis‐induced mitochondrial DNA (mtDNA) together Zn 2+ co‐activate the STING pathway, triggering robust immune response. increases sensitivity to cuproptosis induces immunogenic cell death (ICD) in vivo vitro, which significantly inhibits progression metastasis. The novel strategy of “increasing throttle” (cuproptopsis‐mediated activation & ICD effect) combined “releasing brake” (PD‐L1 inhibition improvement) provides enhancing percutaneous

Язык: Английский

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Advancements in adoptive CAR immune cell immunotherapy synergistically combined with multimodal approaches for tumor treatment

Bioactive Materials, Год журнала: 2024, Номер 42, С. 379 - 403

Опубликована: Сен. 10, 2024

Язык: Английский

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Engineering Bimetallic Polyphenol for Mild Photothermal Osteosarcoma Therapy and Immune Microenvironment Remodeling by Activating Pyroptosis and cGAS‐STING Pathway

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(22)

Опубликована: Май 1, 2024

Abstract The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy existing immunotherapies. Despite attempt novel immune strategies such as checkpoint inhibitors and vaccines, their effectiveness remains suboptimal due inherent difficulty in mitigating ITME simultaneously from both system. promotion anti‐tumor immunity through induction immunogenic cell death activation cGAS‐STING pathway has emerged potential counter stimulate systemic antitumor responses. Here, bimetallic polyphenol‐based nanoplatform (Mn/Fe‐Gallate nanoparticles coated with membranes is presented, MFG@TCM) which combines mild photothermal therapy (PTT) for reversing via inducing pyroptosis OS cells activating dendritic (DCs). immunostimulatory pathways, syngeneic effect, exerted substantial positive impact on promoting secretion damage‐associated molecular patterns (DAMPs) proinflammatory cytokines, favors remodeling microenvironment. Consequently, effector T led notable response, effectively inhibiting growth primary distant tumors. This study proposes new method treating using PTT mudulation, showing promise overcoming current treatment limitations.

Язык: Английский

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Chemical Design Strategy of Ionizable Lipids for In Vivo mRNA Delivery

ChemMedChem, Год журнала: 2024, Номер 19(16)

Опубликована: Май 9, 2024

Lipid nanoparticles (LNPs) are the most clinically successful drug delivery systems that have accelerated development of mRNA drugs and vaccines. Among various structural components LNPs, more recent attention has been paid in ionizable lipids (ILs) was supposed as key component determining effectiveness LNPs for vivo delivery. ILs typically comprised three moieties including heads, linkers, hydrophobic tails, which suggested combination different functional groups could produce with diverse chemical structures biological identities. In this concept article, we provide a summary design strategy high-performing IL candidates discuss their structure-activity relationships shifting tissue-selective We also propose an outlook next-generation ILs, enabling broader translation formulated LNPs.

Язык: Английский

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Tannic acid-based metal-phenolic networks as a versatile platform to mediate cell therapy

Science China Materials, Год журнала: 2024, Номер 67(12), С. 3833 - 3848

Опубликована: Ноя. 7, 2024

Язык: Английский

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Polyphenolic Nanomedicine Regulating Mitochondria REDOX for Innovative Cancer Treatment

Pharmaceutics, Год журнала: 2024, Номер 16(8), С. 972 - 972

Опубликована: Июль 23, 2024

Cancer remains a highly lethal disease globally. The approach centered on REDOX-targeted mitochondrial therapy for cancer has displayed notable benefits. Plant polyphenols exhibit strong REDOX and anticancer properties, particularly by affecting function, yet their structural instability low bioavailability hinder utility. To overcome this challenge, researchers have utilized the inherent physical chemical characteristics of derivatives to develop innovative nanomedicines targeting mitochondria. This review examines construction strategies properties various types polyphenol-based biological nanomedicine regulating mitochondria in recent years, such as polyphenol self-assembly, metal–phenol network, polyphenol–protein, polyphenol–hydrogel, polyphenol–chitosan, polyphenol–liposome. These polyphenolic incorporate enhanced features improved solubility, efficient photothermal conversion capability, regulation homeostasis, ion adsorption through diverse strategies. focus is how these promote ROS production mechanism inhibit cancer. Furthermore, it delves into benefits applications treatments, well challenges future research.

Язык: Английский

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Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform ‘cold’ tumors into ‘hot’ tumors

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Дек. 23, 2024

Язык: Английский

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Facile and rapid fabrication of a novel 3D-printable, visible light-crosslinkable and bioactive polythiourethane for large-to-massive rotator cuff tendon repair

Bioactive Materials, Год журнала: 2024, Номер 37, С. 439 - 458

Опубликована: Апрель 25, 2024

Facile and rapid 3D fabrication of strong, bioactive materials can address challenges that impede repair large-to-massive rotator cuff tears including personalized grafts, limited mechanical support, inadequate tissue regeneration. Herein, we developed a facile methodology generates visible light-crosslinkable polythiourethane (PHT) pre-polymer resin (∼30 min at room temperature), yielding 3D-printable scaffolds with tendon-like attributes capable delivering tenogenic factors. Ex vivo characterization confirmed successful fabrication, robust human supraspinatus tendon (SST)-like tensile properties (strength: 23 MPa, modulus: 459 least 10,000 physiological loading cycles without failure), excellent suture retention (8.62-fold lower than acellular dermal matrix (ADM)-based clinical graft), slow degradation, controlled release fibroblast growth factor-2 (FGF-2) transforming factor-β3 (TGF-β3). In vitro studies showed cytocompatibility factor-mediated tenogenic-like differentiation mesenchymal stem cells. demonstrated biocompatibility (3-week mouse subcutaneous implantation) ability factor-containing to notably regenerate 1-cm native-like biomechanical as uninjured shoulder (8-week, gap rabbit injury). This study demonstrates use 3D-printable, material provide support pro-regenerative cues for challenging injuries such tears.

Язык: Английский

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Engineering live cell surfaces with polyphenol-functionalized nanoarchitectures

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Polyphenol-functionalized nanoarchitectures (cytoPNAs) provide a modular and cell independent strategy to create biohybrids for engineering, with improved production biomanufacturing enhanced efficacy cell-based therapies.

Язык: Английский

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