Manganese-Based Immunostimulatory Metal–Organic Framework Activates the cGAS-STING Pathway for Cancer Metalloimmunotherapy DOI

Sui-Juan Zheng,

Mingfang Yang,

Jia‐Qi Luo

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(16), P. 15905 - 15917

Published: Aug. 11, 2023

Metal-organic frameworks (MOFs) show tremendous promise for drug delivery due to their structural and functional versatility. However, MOFs are usually used as biologically inert carriers in most cases. The creation of intrinsically immunostimulatory remains challenging. In this study, a facile green synthesis method is proposed the preparation manganese ion (Mn2+)-based MOF (ISAMn-MOF) cancer metalloimmunotherapy. ISAMn-MOF significantly facilitates activation cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) related signaling pathways bone-marrow-derived dendritic cells (BMDCs). BMDCs treated with secrete 4-fold higher type I 2- 16-fold proinflammatory cytokines than those equivalent MnCl2. alone or its combination immune checkpoint antibodies suppresses tumor growth metastasis prolongs mouse survival. Mechanistic studies indicate that treatment infiltration stimulatory tumors lymphoid organs. This study provides insight into design bioactive improved

Language: Английский

Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy DOI Creative Commons
Qiang Lü,

Dongquan Kou,

Shenghan Lou

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 2, 2024

Abstract Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, immune cells, plays a crucial role response modulation. Nanoparticles, engineered to reshape TME, shown promising results enhancing by facilitating targeted These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, encourage T infiltration. Biomimetic further enhance increasing internalization agents cells such as cells. Moreover, exosomes, whether naturally secreted body or bioengineered, been explored regulate TME immune-related affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated pH, redox, light conditions, exhibit potential accelerate co-application with checkpoint inhibitors is an emerging strategy boost anti-tumor immunity. With their ability induce long-term immunity, nanoarchitectures are structures development. This review underscores critical overcoming current driving advancement modification.

Language: Английский

Citations

148
Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy DOI Creative Commons
Liang Zhang, An Song,

Qi‐Chao Yang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 2, 2023

Immunogenic programmed cell death, such as pyroptosis and ferroptosis, efficiently induces an acute inflammatory response boosts antitumor immunity. However, the exploration of dual-inducers, particularly nonmetallic inducers, capable triggering both ferroptosis remains limited. Here we show construction a covalent organic framework (COF-919) from planar twisted AIEgen-based motifs dual-inducer for efficient Mechanistic studies reveal that COF-919 displays stronger near-infrared light absorption, lower band energy, longer lifetime to favor generation reactive oxygen species (ROS) photothermal conversion, pyroptosis. Because its good ROS production capability, it upregulates intracellular lipid peroxidation, leading glutathione depletion, low expression peroxidase 4, induction ferroptosis. Additionally, by effectively inhibits tumor metastasis recurrence, resulting in over 90% growth inhibition cure rates exceeding 80%.

Language: Английский

Citations

99
Preparation of magnetic three-dimensional porous Co-rGO aerogel for enhanced microwave absorption DOI

Kunyao Cao,

Xin Yang, Yue Zhang

et al.

Carbon, Journal Year: 2023, Volume and Issue: 208, P. 111 - 122

Published: March 23, 2023

Language: Английский

Citations

66
Sodium Bicarbonate Nanoparticles for Amplified Cancer Immunotherapy by Inducing Pyroptosis and Regulating Lactic Acid Metabolism DOI
Binbin Ding, Pan Zheng, Jia Tan

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(40)

Published: Aug. 17, 2023

Abstract Although immunotherapy has a broad clinical application prospect, it is still hindered by low immune responses and immunosuppressive tumor microenvironment. Herein, simple drug‐free inorganic nanomaterial, alkalescent sodium bicarbonate nanoparticles (NaHCO 3 NPs), prepared via fast microemulsion method for amplified cancer immunotherapy. The obtained NaHCO regulates lactic acid metabolism through acid‐base neutralization so as to reverse the mildly acidic environment. Additionally, can further release high amounts of Na + ions inside cells induce surge in intracellular osmolarity, thus activate pyroptosis pathway immunogenic cell death (ICD), damage‐associated molecular patterns (DAMPs) inflammatory factors, improve responses. Collectively, NPs observably inhibit primary/distal growth metastasis remitted immunosuppression induced activation, showing an enhanced antitumor immunity efficiency. This work provides new paradigm mediated treatment, which potential

Language: Английский

Citations

62
Bioorthogonal Disruption of Pyroptosis Checkpoint for High-Efficiency Pyroptosis Cancer Therapy DOI
Bin Zhang, Zhengwei Liu, Jiawei Zhu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(30), P. 16658 - 16668

Published: July 24, 2023

Pyroptosis is an inflammatory form of programmed cell death that holds great promise in cancer therapy. However, autophagy as the crucial pyroptosis checkpoint and self-protective mechanism cells significantly weakens therapeutic efficiency. Here, a bioorthogonal nanoregulator constructed to induce disrupt checkpoint, enabling high-efficiency The allows situ synthesis accumulation photosensitizer PpIX mitochondria directly produce mitochondrial ROS, thus triggering pyroptosis. Meanwhile, generated inhibitor via palladium-catalyzed chemistry can boost efficacy. With biomimetic membrane coating, this platform for modulating presents specificity poses no harm normal tissue, resulting highly efficient safe antitumor treatment. To our knowledge, first report on disrupting intrinsic protective tumor This work highlights plays key regulative role therapy, which would motivate future design regimens.

Language: Английский

Citations

61
Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle DOI
Le Tu,

Chonglu Li,

Qihang Ding

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 8991 - 9003

Published: March 21, 2024

Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects deep-seated tumors remains challenging. Herein, we introduce a novel self-assembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λem = 1105 nm), as first example Ru(II) supramolecular ICD inducer. synergistically potentiates immunomodulatory and reduces adverse through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting tumor cells, precision organelle localization, improved penetration/retention capabilities. Specifically, demonstrates excellent depth-activated ROS production (∼1 cm), resistance to diffusion, anti-ROS quenching. Moreover, exhibits promising results cellular uptake generation cancer cells multicellular spheroids. Importantly, induces more efficient an ultralow dose (10 μM) compared conventional agent, oxaliplatin (300 μM). In vivo experiments further confirm Ru1105's potency inducer, eliciting CD8+ T depleting Foxp3+ effects. Our research lays foundation for design secure exceptionally potent metal-based agents immunotherapy.

Language: Английский

Citations

47
Utilization of Functionalized Metal–Organic Framework Nanoparticle as Targeted Drug Delivery System for Cancer Therapy DOI Creative Commons
Vy Anh Tran, Van Thuan Le, Van‐Dat Doan

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(3), P. 931 - 931

Published: March 13, 2023

Cancer is a multifaceted disease that results from the complex interaction between genetic and environmental factors. mortal with biggest clinical, societal, economic burden. Research on better methods of detection, diagnosis, treatment cancer crucial. Recent advancements in material science have led to development metal–organic frameworks, also known as MOFs. MOFs recently been established promising adaptable delivery platforms target vehicles for therapy. These constructed fashion offers them capability drug release stimuli-responsive. This feature has potential be exploited therapy externally led. review presents an in-depth summary research conducted date field MOF-based nanoplatforms therapeutics.

Language: Английский

Citations

44
Programmed Targeting Pyruvate Metabolism Therapy Amplified Single‐Atom Nanozyme‐Activated Pyroptosis for Immunotherapy DOI
Rui Niu, Yang Liu, Bo Xu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(24)

Published: Feb. 7, 2024

Abstract Increasing cellular immunogenicity and reshaping the immune tumor microenvironment (TME) are crucial for antitumor immunotherapy. Herein, this work develops a novel single‐atom nanozyme pyroptosis initiator: UK5099 pyruvate oxidase (POx)‐co‐loaded Cu‐NS (Cu‐NS@UK@POx), that not only trigger through cascade biocatalysis to boost of cells, but also remodel immunosuppressive TME by targeting metabolism. By replacing N with weakly electronegative S, original spatial symmetry Cu‐N 4 electron distribution is changed enzyme‐catalyzed process effectively regulated. Compared spatially symmetric nanozymes (Cu‐N SA), S‐doped asymmetric (Cu‐NS SA) exhibit stronger activities, including peroxidase (POD), nicotinamide adenine dinucleotide (NADH) (NOx), L ‐cysteine (LCO), glutathione (GSHOx), which can cause enough reactive oxygen species (ROS) storms pyroptosis. Moreover, synergistic effect SA, UK5099, POx target metabolism, improves increases degree This study provides two‐pronged treatment strategy significantly activate immunotherapy effects via ROS storms, NADH/glutathione/ consumption, oxidation, lactic acid (LA)/ATP depletion, triggering regulating broad vision expanding

Language: Английский

Citations

43
A Vacancy‐Engineering Ferroelectric Nanomedicine for Cuproptosis/Apoptosis Co‐Activated Immunotherapy DOI

Yaqian Du,

Xudong Zhao, Fei He

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(30)

Published: May 4, 2024

Abstract Low efficacy of immunotherapy due to the poor immunogenicity most tumors and their insufficient infiltration by immune cells highlights importance inducing immunogenic cell death activating system for achieving better treatment outcomes. Herein, ferroelectric Bi 2 CuO 4 nanoparticles with rich copper vacancies (named BCO‐V Cu ) are rationally designed engineered ferroelectricity‐enhanced apoptosis, cuproptosis, subsequently evoked immunotherapy. In this structure, suppressed recombination electron–hole pairs band bending polarization lead high catalytic activity, triggering reactive oxygen species bursts apoptosis. The fragments produced apoptosis serve as antigens activate T cells. Moreover, generated charge catalysis, nanomedicine can act “a smart switch” open membrane, promote nanomaterial endocytosis, shut down + outflow pathway evoke thus a strong response is triggered reduced content adenosine triphosphate. Ribonucleic acid transcription tests reveal pathways related activation. Thus, study firstly demonstrates feasible strategy enhancing using single semiconductor‐induced cuproptosis.

Language: Английский

Citations

42
Modulating macrophage phenotype for accelerated wound healing with chlorogenic acid-loaded nanocomposite hydrogel DOI
Shuangqing Wang, Yanhong Liu, Xusheng Wang

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 369, P. 420 - 443

Published: April 5, 2024

Language: Английский

Citations

33