Boosting Peroxidase-Mimetic Activity of FeMn-NC_e Dual-Atom Radiosensitizing Nanozymes for Augmented Radiodynamic Immunotherapy

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Dual-atom nanozymes (DAzymes) have garnered considerable attention as catalysts for reactive oxygen species (ROS)-based therapies, effectively leveraging ROS generation within the tumor microenvironment (TME). Herein, we introduce FeMn-NCe DAzymes, which are meticulously engineered enhanced peroxidase (POD)-mimetic activity and potent radiosensitization to advance radioimmunotherapy. Density functional theory (DFT) calculations reveal that DAzymes lower energy barrier increase substrate affinity, enabling highly efficient catalytic performance. Within TME, these efficiently convert overexpressed hydrogen peroxide (H2O2) into hydroxyl radicals (•OH), potentially activating cGAS-STING immune pathway. This POD-mimetic catalysis is further accelerated under X-ray irradiation, significantly enhancing radiosensitization. Additionally, a uniform coating of ultrasmall gold nanoparticles on enhances absorption cancer cells. The incorporation STING agonist diABZI onto induces long-term antitumor immunity, reprograms immunosuppressive suppresses growth metastasis following single low-dose treatment. work highlights valuable strategy designing radiodynamic immunotherapy.

Language: Английский

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D-bait: A siDNA for regulation of DNA-protein kinases against DNA damage and its implications in cancer

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: 673, P. 125416 - 125416

Published: Feb. 28, 2025

Language: Английский

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A Metformin-Based Multifunctional Nanoplatform as a DNA Damage Amplifier for Maximized Radio-Immunotherapy to Overcome Radiotherapy Resistance

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Radiotherapy (RT) has been highlighted to be an effective strategy for antitumor immunity activation by causing direct DNA damages, but it generally suffers from low response rates due the compromised cytosolic (cDNA) recognition cyclic GMP-AMP synthase (cGAS). Simultaneous repair and clearance system regulation enhanced cDNA accumulation is a useful approach improve immune rates, which remains seldom reported our knowledge. Here, we report construction of metformin (MET)-based multifunctional nanocomplex, CS-MET/siTREX1 (CSMT), consisting biguanide-decorated CS (CS-MET) as vector 3'-5' exonuclease TREX1 siRNA (siTREX1) therapeutic gene RT-induced enhancement amplifying initial damage signals. The uniqueness this study development CSMT specific amplifier promote maximizing radio-immunotherapy circumventing RT resistance. Specifically, nanocomplexes show not only transfection efficiency MET modification also synergistic effects including MET's inhibition on siTREX1's attenuation clearance, leads greatest inhibitory effect in Hepa1-6 proximal/distal tumor model with high growth (TGI) value 99.1% primary significantly distal inducing immunogenic cell death (ICD), promoting tumor-associated neutrophil (TAN) polarization, stimulating tumor-specific memory T-cell generation. Overall, developed herein hold great translatable promises overcoming resistance clinics.

Language: Английский

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Nuclease‐Mimetic Nanomaterials: From Fundamentals to Bioapplications

Small, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Abstract With the rapid development of nanozymes and nanomedicine, designing novel nanostructures directly acting on deoxyribonucleic acid (DNA) has great therapeutic potential because DNA is carrier genetic information plays a vital role life activities organism. Specifically, cleavage an important step in most these engineering technologies. While nucleases play crucial roles cell metabolism by efficient cutting, practical applications natural suffer from some intrinsic shortcomings such as high cost intolerance to harsh environments. In past 20 years, varieties engineered with (nuclease‐mimetic nanomaterials, abbreviated nuclease mimics) have been developed rapidly widely used biomedical fields. view significant progress nuclease‐mimetic possible mechanism mediated nanomaterials systematically discussed this review, classification illustrated. Their applications, especially anti‐biofilms cancer treatment, are also comprehensively summarized. Finally, current opportunities challenges stimulate research understanding nanomaterials.

Language: Английский

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Janus Nanoprobe with Dual-Modal NIR-II Fluorescence/Photoacoustic Imaging for Precision Cancer Radiosensitizing Therapy

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: May 10, 2025

The use of radiotherapy sensitizers has proven to be effective in overcoming tumor resistance and improving treatment efficacy. However, challenges such as poor biocompatibility difficulty accurately guiding with high efficiency still persist. Herein, we propose a radiosensitizer Janus nanostructure address these issues by enabling dual-modal fluorescence (FL)/photoacoustic (PA) imaging the second near-infrared region (NIR-II, 900-1700 nm) for precise efficient guidance. nanoprobes are fabricated initially coating silica (SiO2) on one end gold nanorod (AuNR) aspect ratio, followed situ decoration lanthanide-doped down-conversion nanoparticle (DCNP) shell SiO2, finally modifying it biocompatible polyethylene glycol (PEG), named AuNR@DCNP@PEG. Guided NIR-II FL/PA imaging, AuNR@DCNP@PEG was successfully irradiated at optimal enrichment time point, generating significant amount reactive oxygen species exhibiting excellent sensitization effects vitro vivo. This imaging-guided sensitizer is anticipated offer an approach achieving radiotherapy.

Language: Английский

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Layered-Responsive Multivalent Tetrahedral DNA Framework-Decorated CRISPR-Cas12a Nanocapsule Enables Precise and Enhanced Tumor Chemotherapy

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

The lack of selective tumor targeting and the high toxicity conventional chemotherapy treatments remain major challenges in cancer therapy. Here, we develop a self-controlled DNA nanostructure-CRISPR-12a system, triple-locked cascade therapy nanocapsule (Tatna), for efficient targeted treatment. Tatna integrates structural tetrahedrons (DTs) with drug-loading capacity, Cas12a/crRNA ribonucleoprotein (Cas12a RNP), doxorubicin (DOX) to enable multisite response precise drug delivery augmented By incorporation nucleolin-targeting aptamer, achieves cell internalization. Encapsulation pH-responsive poly l-lactic-co-glycolic acid (PLGA) ensures stable circulation controlled release both DOX Cas12a until tumor-specific activation acidic microenvironment. RNP, triggered by APE1 mRNA overexpression cells, induces trans-cleavage DTs, releasing transport into nucleus induce enhanced apoptosis. This self-regulating multifunctional approach enhances efficacy while reducing off-target effects. Tatna's programmable, system represents powerful strategy advancing precision medicine personalized

Language: Английский

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Carbohydrate polymer-based nanoparticles with cell membrane camouflage for cancer therapy: A review

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 289, P. 138620 - 138620

Published: Dec. 13, 2024

Language: Английский

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