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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Functionalized biomimetic nanoparticles loaded with salvianolic acid B for synergistic targeted triple-negative breast cancer treatment

Materials Today Bio, Год журнала: 2025, Номер 30, С. 101441 - 101441

Опубликована: Янв. 1, 2025

The therapeutic effect of immune checkpoint inhibitors (ICIs) in triple-negative breast cancer (TNBC) is unsatisfactory. "cold" microenvironment caused by tumor-associated fibroblasts (TAFs) has an adverse on the antitumor response. Therefore, this study, mixed cell membrane-coated porous magnetic nanoparticles (PMNPs) were constructed to deliver salvianolic acid B (SAB) induce response, facilitating transition from a "hot" tumor and ultimately enhancing efficacy inhibitors. PMNP-SAB, which based coating red blood membrane TAF (named PMNP-SAB@RTM), can simultaneously achieve dual effects "immune escape" "homologous targeting". Under influence external field (MF), SAB be targeted concentrated at site. released tumors effectively inhibit production extracellular matrix (ECM) TAFs, promote T-cell infiltration, responses. Ultimately, combination PMNP-SAB@RTM BMS-1 (PD-1/PD-L1 inhibitor 1) inhibited growth. Finally, study presents precise effective new strategy for TNBC immunotherapy basis differentiation microenvironments.

Язык: Английский

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Spatial Isolation of Single Copper(I) Sites for Cascade Enzyme‐Like Catalysis and Simultaneous Ferroptosis/Cuproptosis Boosted Immunotherapy

Exploration, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

ABSTRACT Nanozyme‐based immunogenic cell death (ICD) inducers that effectively induce a strong immune response via enzyme‐like process have attracted great attention, but how to ensure controllable active sites and maximize site utilization remains problem. Here, we report structurally well‐defined highly functional single‐site copper(I) nanomodulators termed CuNTD, constructed by precisely anchoring atomically dispersed self‐assembly S‐Cu(I)‐S onto two‐dimensional Ti 3 C 2 surface. Leveraging Cu + with higher catalytic efficiency than 2+ , CuNTD generates reactive oxygen species (ROS) storms through photothermal‐enhanced cascade catalysis, further inducing mitochondrial dysfunction, ferroptosis cuproptosis. Multifunctional triggers ICD cascade‐regulatory pathways of photothermal‐amplified ROS storms, cuproptosis ferroptosis, promoting dendritic maturation while reducing monotherapies side effects resistance. In vivo, combined FDA‐approved immunoadjuvants significantly prolong the survival mice. With its demonstrated biosafety high as an inducer, this study provides promising framework for advancing augmented tumor immunotherapy significant clinical potential.

Язык: Английский

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Endogenous Protein‐Modified Gold Nanorods as Immune‐Inert Biomodulators for Tumor‐Specific Imaging and Therapy

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Abstract Engineered modifications of nanomaterials inspired by nature hold great promise for disease‐specific imaging and therapies. However, conventional polyethylene glycol modification is limited immune system rejection. The manipulation gold nanorods (Au NRs) modified endogenous proteins (eP@Au) reported as an engineered biomodulator enhanced breast tumor therapy. results show that eP@Au NRs neither activate inflammatory factors in vitro nor elicit rejection responses vivo. Tumor‐specific exhibit a dual‐modal capability trigger mild photothermal effect under near‐infrared light irradiation, enabling highly efficient therapy tumors. Transcriptome sequencing confirmatory experiments reveal the antitumor mainly attributed to repression PI3K‐Akt/MAPK signaling pathways at molecular level. This powerful surprising situ eP‐regulated biomodulation demonstrates advantages convenient fabrication, inert immunogenicity, biocompatibility, providing alternative strategy biomedical

Язык: Английский

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Dual-Targeted Assembled Nanodrugs for Near-Infrared Photothermal Immunotherapy of Triple-Negative Breast Cancer

ACS Applied Materials & Interfaces, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 22, 2024

Triple-negative breast cancer (TNBC) is known for its poor prognosis and aggressive behavior, being highly prone to recurrence metastasis, currently has limited effective treatment options. Photothermal therapy (PTT) an emerging, minimally invasive, low-drug-resistance, precisely controllable therapeutic method treatment, offering hope break through the bottleneck in TNBC therapy. The antitumor efficiency of PTT predominantly contingent upon performance photothermal drugs. Therefore, there urgent need develop drugs that not only have excellent conversion but also possess strong tumor-targeting capabilities good biosafety. Here, we developed a tumor-targeted agent with near-infrared (NIR) absorption capability based on strategy biomolecular assembly, utilizing biliverdin manganese complexes (MnBV) amphiphilic phospholipid–polymer conjugates (DSPE-PEG DSPE-PEG-cKNGRE). This assembled drug exhibits uniform size, stability, ideal efficiency. In 4T1 tumor-bearing mouse model TNBC, it shows tumor dual-targeting significant enrichment performance. While ablating primary tumor, further stimulates maturation dendritic cells (DCs), enhancing infiltration T lymphocytes into spleen thus reshaping immune microenvironment thereby effectively inhibiting metastasis recurrence. provides innovative candidate paradigm potential advance precise, targeted, safe invasive malignancies.

Язык: Английский

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Polymer-based delivery systems with metal complexes as contrast agents for medical imaging

Coordination Chemistry Reviews, Год журнала: 2024, Номер 518, С. 216071 - 216071

Опубликована: Июль 10, 2024

Язык: Английский

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Bifunctional cascaded single-atom nanozymes for enhanced photodynamic immunotherapy through dual-depressing PD-L1 and regulating hypoxia

Biomaterials, Год журнала: 2025, Номер 317, С. 123106 - 123106

Опубликована: Янв. 11, 2025

Язык: Английский

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Reprogramming the Tumor Immune Microenvironment with ICAM‐1‐Targeted Antibody‒Drug Conjugates and B7‐H3‐CD3 Bispecific Antibodies

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Abstract Reprogramming the tumor immune microenvironment (TIM) plays an important role in promoting reversal of “cold” tumors into “hot” inflammatory tumors. Improving drug targeting, blocking checkpoints, and activation cells are crucial for reprogramming TIM. Here, intercellular adhesion molecule 1‐targeted antibody‒drug conjugate combination with a B7‐H3‐CD3 bispecific antibody is selected TIM reprogramming, which improved efficacy triple‐negative breast cancer immunotherapy. This therapy improves blocks checkpoint pathways, activates effector T to release cytokines, leading immunogenic cell death tumor‐associated antigens. effect promotes maturation dendritic cells, infiltration cytotoxic CD8+ repolarization M1‐type macrophages, reduction M2‐type suppressor Tregs, MDS thereby In addition, this innovative strategy accumulation at metastasis sites significantly impedes progression lung metastatic lesions. Overall, study provides novel insights using immunotherapeutic strategies that leverage synergistic effects antibody‐drug conjugates antibodies.

Язык: Английский

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Magnesium alloy implant with photothermal-enhanced ferroptosis towards a multimodal therapy strategy for osteosarcoma

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 161350 - 161350

Опубликована: Март 1, 2025

Язык: Английский

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Harnessing Nanoreactors with Coupled Optical and Molecular Modalities for Photoenzymatic Modulation of Active Species in Cancer Photo‐Immunotherapy

Small, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

The dynamic process in tumor ablation requires both the generation of reactive oxygen species (ROS) to elicit immunogenic cell death (ICD) and subsequent reduction ROS levels maintain stimulatory activity signaling proteins recover T cells' immune function. Inspired by regulation mechanism redox homeostasis myeloid-derived suppressor cells high-selectivity alcohols/aldehydes conversions 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) Fe(III) synergistic catalysis, photoenzymatic modulators with contradictory but functions are developed for adaptive photo-immunotherapy cancer. In particular, poly(caffeic acid) (PCA) nanospheres synthesized highly efficient oxidative polymerization CA. obtained π-conjugated structures have an extended absorbance near-infrared (NIR) region, narrow band energy (0.86 eV), low exciton binding (43.56 meV) that lead polymerization-enhanced type I photosensitization photostability. Meanwhile, abundant semiquinone radicals existing PCA bestow them superior antioxidant Under NIR irradiation, elevated superoxide radical yields (3.5-fold compared CA) heat stress robust ICD. When irradiation ceases, active downregulation infiltration lymphocytes increase 2.7-fold conventional photosensitizers. As envisaged, this work demonstrates a novel tactic remodel effective inhibition growth metastasis.

Язык: Английский

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