Dual-Enzyme-Instructed Peptide Self-Assembly to Boost Immunogenic Cell Death by Coordinating Intracellular Calcium Overload and Chemotherapy

ACS Nano, Год журнала: 2025, Номер 19(1), С. 488 - 503

Опубликована: Янв. 4, 2025

The concept of immunogenic cell death (ICD) induced by chemotherapy as a potential synergistic modality for cancer immunotherapy has been widely discussed. Unfortunately, most chemotherapeutic agents failed to dictate effective ICD responses due their defects in inducing potent signaling. Here, we report dual-enzyme-instructed peptide self-assembly platform CPMC (CPT-GFFpY-PLGVRK-Caps) that cooperatively utilizes camptothecin (CPT) and capsaicin (Caps) promote engage systemic adaptive immunity tumor rejection. Although CPT Caps respectively prevent progression inhibiting type-I DNA topoisomerase activating transient receptor cation channel subfamily V member 1 (TRPV1) intracellular calcium overload, neither alone effectively stimulates sufficient signaling meet immunotherapeutic needs. CPMC, sequentially allowing an active derivative VRK-Caps release extracellularly intracellularly, can synergize two distinct apoptosis pathways stimulated increase immunogenicity elicit T-cell-based immunity. Consequently, facilitates the generation improved tumor-specific cytotoxic T-cell sustained immunological memory, successfully suppressing both primary distant tumors. Moreover, render tumors susceptible PD-L1 blockade with antiprogrammed death-ligand (aPDL1) antibody inhibition. Combining drugs low ICD-stimulating capacity using strategy was demonstrated boost potentiate immunotherapy.

Язык: Английский

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Metal-Organic Layer Delivers 3-Bromopyruvate to Mitochondria for Metabolic Regulation and Cancer Radio-Immunotherapy

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Abnormal cancer metabolism causes hypoxia and immunosuppression, limiting the anti-tumor efficacy of radiotherapy. Herein, we report a positively charged, mitochondria-targeted nanoscale metal-organic layer conjugated with 3-bromopyruvate (BP), BP/Hf12-Ir, for metabolic reprogramming radiosensitization. BP/Hf12-Ir disrupts oxidative phosphorylation glycolysis, reducing energy production alleviating to enhance radiotherapy immunity. in combination X-ray irradiation inhibits tumor growth by 95% prevents lung metastasis mouse models. When further combined immune checkpoint blockade, this treatment induces robust immunity, achieving 98% inhibition.

Язык: Английский

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Self-Assembling Nucleopeptides Exhibiting Strong Antimicrobial Activity against Multidrug-Resistant Clinically Isolated Strains and In Vitro Wound Healing Compatibility

ACS Applied Bio Materials, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

To combat the emerging threat of antimicrobial resistance (AMR), in this study, two amphiphilic nucleopeptides (NPs) were synthesized by conjugating nucleobase thymine with peptide amphiphiles. These compounds fully characterized using various analytical techniques. Notably, both formed hydrogels milli-Q water at neutral pH (pH 6.9). X-ray diffraction further confirmed antiparallel β-sheet-like structures, along aromatic π–π stacking and hydrogen-bonding (H-bonding) interactions between moieties gel phase. Field emission gun transmission electron microscopy revealed a nanofibrillar network structure these self-assembled peptides. A significant feature supramolecular self-assemblies is their potent activity against types bacteria, such as Gram-positive Gram-negative standard American Type Culture Collection (ATCC) including Bacillus subtilis, Escherichia coli, multidrug-resistant clinically isolated ATCC strains methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Pseudomonas aeruginosa. Among these, peptides demonstrated remarkable inhibition MRSA (MIC: 15.92–16.86 μM) K. pneumoniae 8.8–50 μM), highlighting potential agents deadly (MDR) bacteria. Additionally, assemblies found to be highly biocompatible, MTT assays on HEK-293 cells, showing IC50 values range 0.5–1.1 mM. In an vitro wound healing assay HeLa fluorescence that treatment did not disrupt cell or mitochondrial membranes cells. This work presents broad-spectrum efficacy MDR demonstrates high biocompatibility, supporting use agents.

Язык: Английский

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Self-Reporting Ratiometric AIEgen-Peptide Nanoprobes for Activatable Chemotherapy and Noninvasive Imaging of Therapeutic Outcomes

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Efficacious chemotherapy and real-time therapeutic monitoring remain major challenges in cancer treatment. Traditional systems often lack tumor specificity, limiting efficacy, hindering therapy optimization. Moreover, the absence of can lead to missed opportunities increased risks side effects. Herein, we designed a self-reporting ratiometric AIEgen-peptide nanoprobe (TPE-1(Hyd-DOX)-DEVD) for activatable noninvasive imaging outcomes. When doxorubicin (DOX) is selectively activated acidic microenvironment, ensuing caspase-3 cascade triggers morphological transformation that amplifies TPE fluorescence. This enhancement allows TPE/DOX fluorescence ratio serve as an indicator DOX activation providing feedback. Both vitro vivo studies demonstrated TPE-1(Hyd-DOX)-DEVD exhibited impressive suppression efficacy excellent biocompatibility. study highlights strong potential this valuable tool theranostics, offering hope more effective personalized treatment strategies.

Язык: Английский

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Alkaline Phosphatase and ATG4B Sequentially Activated Fluorescent Probe for Cancer Cell-Specific Live Imaging of Autophagy

Analytical Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Tracking autophagy in cancer cells is crucial for enhancing therapies. Existing methods are often inefficient and cannot distinguish from normal during autophagy. Herein, a sequentially activated peptide probe, NBD-1p-Dabcyl, was developed achieving cell-specific imaging of The probe self-assembled fluoresced brightly upon sequential processing by alkaline phosphatase (ALP) autophagy-related protease (ATG4B), where NBD-1p-Dabcyl dephosphorylated ALP to give NBD-1-Dabcyl, which then processed ATG4B into nanofibers emitting strong fluorescence. Notably, the bright fluorescence NBD observed MDA-MB-231 HeLa, while NIH3T3 exhibited weaker fluorescence, allowing differentiation between using rapamycin (Rap)-induced cell model. enhanced attributed higher activities intracellular ATG4B. Next, used assess inhibition efficiency an inhibitor NSC 185058 cells, correlation intensity concentration suggested that could predict activity inhibitors. Finally, animal experiments revealed effectively facilitated situ tumor tissues. design this offers practical approach monitoring enabling high-throughput screening inhibitors therapy.

Язык: Английский

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Self‐Assembly of Noncanonical Peptides: A New Frontier in Cancer Therapeutics and Beyond

Macromolecular Bioscience, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Abstract In addition to the 20 standard amino acids that form building blocks of proteins, nature employs alternative create specialized “noncanonical peptides.” These unique peptides, found in organisms from bacteria humans, often exhibit unconventional structures and functionalities, playing critical roles modulating cellular processes, particularly as antibiotics. Their potential has attracted significant interest for designing novel functional materials based on noncanonical peptides. This review highlights recent advances generation application peptide assemblies. It begins with a definition including classic examples showcase their distinct useful biological activities. Then applications assemblies developing anticancer therapeutics are discussed, focusing representative studies demonstrate efficacy versatility targeting tumor cells. Beyond oncology, it is explored how have been utilized biomaterials, regenerative medicine, molecular imaging catalysis. Finally, perspectives offered future directions this rapidly evolving field, emphasizing exciting opportunities remaining challenges will drive continued innovation applying peptide‐based

Язык: Английский

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Advances in the design of π-conjugated peptide assemblies

Trends in Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Folic Acid-Functionalized β-Cyclodextrin for Delivery of Organelle-Targeted Peptide Chemotherapeutics in Cancer

Molecular Pharmaceutics, Год журнала: 2024, Номер 21(9), С. 4498 - 4509

Опубликована: Июль 29, 2024

Recent emphasis on the design of drug delivery systems typically involves effective transport a pharmaceutical substance to disease site with desired therapeutic efficacy and minimal cytotoxicity. Organelle-targeted peptides have become an integral part designing important class prodrug/prodrug assemblies for new supramolecular therapeutics owing their favorable biocompatibility, synthetic ease, tunability aggregation behavior, functionalization site-specificity. However, it is still limited due low selectivity. We designed folic acid-functionalized β-cyclodextrin (FA-CD) as platform specific selective organelle-targeted (such microtubule, lysosome, mitochondria) peptide chemotherapeutics folate receptor (FR) overexpressing cancer cell lines. Low toxicity was found FA-CD inclusion complex in FR-negative normal cells, but superior inhibition tumor growth no vivo xenograft model.

Язык: Английский

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Multifunctional Nanomaterials Mediate Cholesterol Depletion for Cancer Treatment

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(46)

Опубликована: Авг. 15, 2024

Abstract Cholesterol is an essential membrane component, and the metabolites from cholesterol play important biological functions to intricately support cancer progression dampen immune responses. Preclinical clinical studies have demonstrated role of metabolism regulation on inhibiting tumor growth, remodeling immunosuppressive microenvironment (TME), enhancing anti‐tumor immunity. In this minireview, we discuss complex in tumors, its progression, influences cells TME. We provide overview recent advances treatment through regulating metabolism. design cholesterol‐altering multifunctional nanomaterials regulate oxidative stress, modulate checkpoints, manipulate mechanical stress responses, alter metabolic pathways. Additionally, examine interactions between established treatments with aim identifying efficient strategies disrupt synergistic combination therapies for effective treatment.

Язык: Английский

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Fibroblast Growth Factor Receptor 1-Specific Dehydrogelation to Release Its Inhibitor for Enhanced Lung Tumor Therapy

ACS Nano, Год журнала: 2024, Номер 18(42), С. 29223 - 29232

Опубликована: Окт. 11, 2024

Fibroblast growth factor receptor 1 (FGFR1) is emerging as a promising molecular target of lung cancer, and various FGFR1 inhibitors have exhibited significant therapeutic effects on cancer in preclinical research. Due to their low targeting ability or bioavailability, direct administration these may cause side effects. Herein, hydrogelator, Nap-Phe-Phe-Phe-Glu-Thr-Glu-Leu-Tyr-OH (

Язык: Английский

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