Augmenting Immunotherapy via Bioinspired MOF‐Based ROS Homeostasis Disruptor with Nanozyme‐Cascade Reaction

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(49)

Published: Sept. 10, 2023

Despite its remarkable clinical breakthroughs, immune checkpoint blockade (ICB) therapy remains limited by the insufficient response in "cold" tumor. Nanozyme-based antitumor catalysis is associated with precise activation tumor microenvironment (TME). In this study, a cascade-augmented nanoimmunomodulator (CMZM) multienzyme-like activities, which includes superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione oxidase (GSHOx), that dissociates under an acidic abundant GSH TME, proposed for multimodal imaging-guided chemodynamic (CDT)/photodynamic (PDT) enhanced immunotherapy. Vigorous activities can not only produce O2 to alleviate hypoxia promote polarization of M2 M1 macrophages, but also generate ROS (•OH 1 ) deplete TME expose necrotic cell fragments reverse immunosuppressive eliciting maturation dendritic cells infiltration cytotoxic T lymphocytes (CTLs) tumors. Therefore, inhibitory effects on both primary distant tumors are achieved through synergy α-PD-L1 blocking antibody. This cascade multienzyme-based nanoplatform provides smart strategy highly efficient ICB immunotherapy against revising TME.

Language: Английский

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Nanomedomics

ACS Nano, Journal Year: 2024, Volume and Issue: 18(17), P. 10979 - 11024

Published: April 18, 2024

Nanomaterials have attractive physicochemical properties. A variety of nanomaterials such as inorganic, lipid, polymers, and protein nanoparticles been widely developed for nanomedicine via chemical conjugation or physical encapsulation bioactive molecules. Superior to traditional drugs, nanomedicines offer high biocompatibility, good water solubility, long blood circulation times, tumor-targeting Capitalizing on this, several nanoformulations already clinically approved many others are currently being studied in clinical trials. Despite their undoubtful success, the molecular mechanism action vast majority remains poorly understood. To tackle this limitation, herein, review critically discusses strategy applying multiomics analysis study nanomedicines, named nanomedomics, including advantages, applications, future directions. comprehensive understanding could provide valuable insight therefore foster development translation nanomedicines.

Language: Английский

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Sulfatase-Induced In Situ Formulation of Antineoplastic Supra-PROTACs

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(15), P. 10753 - 10766

Published: April 5, 2024

Proteolysis targeting chimera (PROTAC) technology is an innovative strategy for cancer therapy, which, however, suffers from poor delivery and limited capability protein of interest (POI) degradation. Here, we report a the in situ formulation antineoplastic Supra-PROTACs via intracellular sulfatase-responsive assembly peptides. Coassembling sulfated peptide with two ligands binding to ubiquitin VHL Bcl-xL leads formation pro-Supra-PROTAC, which ratio rationally optimized based on their affinity. The resulting pro-Supra-PROTAC precisely undergoes enzyme-responsive into nanofibrous cells overexpressing sulfatase. Mechanistic studies reveal that pro-Supra-PROTACs selectively cause apparent cytotoxicity through degradation activation caspase-dependent apoptosis, during ligand improves bioactivity POI cell death. In vivo show enhanced tumor accumulation retention pro-Supra-PROTACs, as well inhibiting growth excellent biosafety when coadministrating chemodrugs. Our findings provide new approach enzyme-regulated peptides living development PROTACs high delivering efficiency.

Language: Английский

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Tandem-controlled lysosomal assembly of nanofibres induces pyroptosis for cancer immunotherapy

Nature Nanotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Language: Английский

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A comprehensive review on peptide-bearing biomaterials: From ex situ to in situ self-assembly

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 502, P. 215600 - 215600

Published: Dec. 14, 2023

Language: Английский

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A Novel NQO1 Enzyme-Responsive Polyurethane Nanocarrier for Redox-Triggered Intracellular Drug Release

Biomacromolecules, Journal Year: 2023, Volume and Issue: 24(5), P. 2225 - 2236

Published: April 11, 2023

The design of nano-drug delivery vehicles responsive to tumor microenvironment stimuli has become a crucial aspect in developing cancer therapy recent years. Among them, the enzyme-responsive system is particularly effective, as it utilizes tumor-specific and highly expressed enzymes precise targets, leading increased drug release at target sites, reduced nonspecific release, improved efficacy while minimizing toxic side effects on normal tissues. NAD(P)H:quinone oxidoreductase 1 (NQO1) an important reductase associated with overexpressed some cells, lung breast cancer. Thus, nanocarriers high selectivity responsiveness NQO1 great significance for diagnosis treatment. It been reported that under physiological conditions, can specifically reduce trimethyl-locked benzoquinone structure through two-electron reduction, resulting rapid lactonization via enzymatic reaction. Based this, novel reduction-sensitive polyurethane (PEG-PTU-PEG) block copolymer was designed synthesized by copolymerizing diisocyanate, monomer (TMBQ), poly(ethylene glycol). successful synthesis monomers polymers verified nuclear magnetic resonance (1H NMR) gel permeation chromatography (GPC). Then, PEG-PTU-PEG micelles were successfully prepared self-assembly, their reductive dissociation behavior presence Na2S2O4 dynamic light scattering (DLS), 1H NMR, GPC. Next, model doxorubicin (DOX) encapsulated into hydrophobic core this microemulsion method. observed drug-loaded could also achieve redox response rapidly substances. In vitro cell experiments demonstrated had good biocompatibility low hemolysis rate (<5%). Furthermore, enzyme inhibitor (dicoumarol), lower from A549 4T1 cells both fluorescence microscopy flow cytometry assays, but not NIH-3T3 control cells. Predictably, DOX-loaded showed cytotoxicity inhibitors. These results indicate accomplish specific reducing environment enzymes. Therefore, study provides new option construction targeting which benefit intracellular drug-specific precision tumors.

Language: Английский

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Nanotechnology in inflammation: cutting-edge advances in diagnostics, therapeutics and theranostics

Theranostics, Journal Year: 2024, Volume and Issue: 14(6), P. 2490 - 2525

Published: Jan. 1, 2024

Inflammatory dysregulation is intimately associated with the occurrence and progression of many life-threatening diseases.Accurate detection timely therapeutic intervention on inflammatory are crucial for effective therapy inflammation-associated diseases.However, clinical outcomes inflammation-involved disorders still unsatisfactory.Therefore, there an urgent need to develop innovative anti-inflammatory strategies by integrating emerging technological innovations traditional therapeutics.Biomedical nanotechnology one promising fields that can potentially transform diagnosis treatment inflammation.In this review, we outline recent advances in biomedical inflammation, special attention paid nanosensors nanoprobes precise inflammation-related diseases, nanotherapeutics, as well nanotheranostics combined applications.Moreover, prospects challenges translation nanomedicines highlighted.

Language: Английский

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Inflammatory Microenvironment-Responsive Nanomicelles for Acute Lung Injury Therapy: ROS-Scavenging and Macrophage Repolarization

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101622 - 101622

Published: Feb. 27, 2025

Language: Английский

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Design of Stimuli‐Responsive Peptides and Proteins

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 33(7)

Published: Dec. 7, 2022

Abstract Stimuli‐responsive peptides and proteins are an exciting class of smart biomaterials for various applications have received significant attention over the past decades. A wide variety stimuli such as temperature, pH, ions, enzymes, magnetic field, redox, etc., explored. This article provides a review five intensively studied types stimuli‐responsive proteins, their design principles applications, including temperature‐, pH‐, light‐, metal ion‐, enzyme‐responsive with emphasis on key concepts switch function. Moreover, typical examples discussed to provide better understanding concept underlying methodology. will facilitate inspire future innovation toward new peptide‐ protein‐based materials diverse applications.

Language: Английский

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Light-Triggered Self-Assembly of Peptide Nanoparticles into Nanofibers in Living Cells through Molecular Conformation Changes and H-Bond Interactions

ACS Nano, Journal Year: 2022, Volume and Issue: 16(11), P. 18978 - 18989

Published: Nov. 10, 2022

Controlled self-assembly has attracted extensive interest in biological and nanotechnological applications. Enzymatic or biocatalytic triggered is widely used for the diagnostic prognostic marker different pathologies because of their nanostructures effects. However, it remains a great challenge to control peptides living cells with high degree spatial temporal precision. Here we demonstrate light-triggered platform that enables spatiotemporal from nanoparticles into nanofibers through subtle molecular conformational changes internal H-bonding interactions. The contained 3-methylene-2-(quinolin-8-yl) isoindolin-1-one, which acts as light-controlled unit disrupt hydrophilic/lipophilic balance change conformation, peptide can be faster recombinant assemble via process good biocompatibility does not involve waste generation oxygen consumption; moreover, assembly rate constant was fast up 0.17 min–1. It applied regulation cells. As such, our findings controllable initiative regulating cellular behaviors systems.

Language: Английский

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