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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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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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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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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