Nitric Oxide Induces Immunogenic Cell Death and Potentiates Cancer Immunotherapy

ACS Nano, Journal Year: 2022, Volume and Issue: 16(3), P. 3881 - 3894

Published: March 3, 2022

Tumor cells undergoing immunogenic cell death (ICD) release damage-associated molecular patterns (DAMPs) to trigger a long-term protective antitumor response. ICD can be induced by certain pathogens, chemotherapeutics, and physical modalities. In this work, we demonstrate that gaseous molecule, specifically nitric oxide (NO), induce potent effect. NO exerts cytotoxic effects are accompanied the emission of DAMPs based on endoplasmic reticulum stress mitochondrial dysfunction pathways. Released elicit immunological protection against subsequent rechallenge syngeneic tumor in immunocompetent mice. We prepare polynitrosated polyesters with high storage capacity through facile polycondensation reaction followed postsynthetic modification. The polyesters-based nanogenerator (NanoNO) enables efficient delivery controlled tumors induces sufficient different immune-intact models tumors, NanoNO exhibits significant growth suppression increases local dose signals T infiltrations, ultimately prolonging survival. addition, synergizes PD-1 blockade prevent metastasis. conclude not only is inducer for cancer immunotherapy but also it expands range inducers into field molecules.

Language: Английский

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Advanced Nitric Oxide Generating Nanomedicine for Therapeutic Applications

ACS Nano, Journal Year: 2023, Volume and Issue: 17(10), P. 8935 - 8965

Published: May 1, 2023

Nitric oxide (NO), a gaseous transmitter extensively present in the human body, regulates vascular relaxation, immune response, inflammation, neurotransmission, and other crucial functions. Nitrite donors have been used clinically to treat angina, heart failure, pulmonary hypertension, erectile dysfunction. Based on NO's vast biological functions, it further can tumors, bacteria/biofilms infections, wound healing, eye diseases, osteoporosis. However, delivering NO is challenging due uncontrolled blood circulation release half-life of under five seconds. With advanced biotechnology development nanomedicine, packaged with multifunctional nanocarriers by physically embedding or chemically conjugating reported show improved therapeutic efficacy reduced side effects. Herein, we review discuss recent applications nanomedicines, their mechanisms, challenges nanomedicines for future scientific studies clinical applications. As enables inhibition replication DNA RNA infectious microbes, including COVID-19 coronaviruses malaria parasites, highlight potential antipandemic efforts. This aims provide deep insights practical hints into design strategies nanomedicines.

Language: Английский

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Copper Single-Atom Jellyfish-like Nanomotors for Enhanced Tumor Penetration and Nanocatalytic Therapy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(7), P. 6789 - 6799

Published: March 29, 2023

Single-atom catalysts with extraordinary catalytic activity have been receiving great attention in tumor therapy. However, most single-atom lack self-propulsion properties, restricting them from actively approaching cancer cells or penetrating the interior of tumors. Herein, we design N-doped jellyfish-like mesoporous carbon nanomotors coordinated copper (Cu-JMCNs). It is a combination nanocatalytic medicine and nanomotor for The Cu single atom can catalyze H2O2 into toxic hydroxyl radical (•OH) chemodynamic therapy (CDT). Near-infrared light triggers Cu-JMCNs to achieve self-thermophoretic motion because asymmetric structure photothermal property carbon, which significantly improves cellular uptake penetration three-dimensional In vivo experiments indicate that CDT near-infrared propulsion over 85% inhibition rate. This work sheds on development advanced biomedical applications.

Language: Английский

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Extracellular vesicles and their engineering strategies, delivery systems, and biomedical applications

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 365, P. 1089 - 1123

Published: Jan. 1, 2024

Language: Английский

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Carrier-Free Trehalose-Based Nanomotors Targeting Macrophages in Inflammatory Plaque for Treatment of Atherosclerosis

ACS Nano, Journal Year: 2022, Volume and Issue: 16(3), P. 3808 - 3820

Published: Feb. 24, 2022

Inducing autophagy of macrophages to improve abnormal lipid metabolism is an important way treat atherosclerosis (AS). Yet, the current application mammalian target rapamycin (mTOR)-dependent inducers limited by side effects and lack targeting low biological availability. Herein, a kind nitric oxide (NO)-driven carrier-free nanomotor based on reaction between trehalose (Tr, one mTOR-independent inducers), L-arginine (Arg), phosphatidylserine (PS) reported. The developed nanomotors use NO as driving force, which generated from Arg excessive reactive oxygen species (ROS) inducible synthase (iNOS) specifically presenting in AS microenvironment. high expression ROS iNOS site can be used chemoattractants induce chemotaxis behavior achieve first-step plaque. Subsequently, "eat me" signal sent PS exploited precisely plaque, realizing plaque-macrophage-targeted effect this step-by-step strategy. In vitro vivo results confirm that introduction concept has greatly improved availability (the dose reduced 2.5 g kg-1 previous reports 0.01 work). Particularly, consumed production during process also play positive roles, former regulates M2 polarization latter promotes reconstruction endothelial barrier, contributes multilink treatment AS.

Language: Английский

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Medical micro- and nanomotors in the body

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(2), P. 517 - 541

Published: Oct. 13, 2022

Attributed to the miniaturized body size and active mobility, micro- nanomotors (MNMs) have demonstrated tremendous potential for medical applications. However, from bench bedside, massive efforts are needed address critical issues, such as cost-effective fabrication, on-demand integration of multiple functions, biocompatibility, biodegradability, controlled propulsion in vivo navigation. Herein, we summarize advances biomedical MNMs reported past two decades, with particular emphasis on design, propulsion, navigation, abilities biological barriers penetration, biosensing, diagnosis, minimally invasive surgery targeted cargo delivery. Future perspectives challenges discussed well. This review can lay foundation future direction MNMs, pushing one step forward road achieving practical theranostics using MNMs.

Language: Английский

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Artificial nanomotors: Fabrication, locomotion characterization, motion manipulation, and biomedical applications

Interdisciplinary materials, Journal Year: 2022, Volume and Issue: 1(2), P. 256 - 280

Published: April 1, 2022

Abstract Artificial nanomotors are nanoscale machines capable of converting surrounding other energy into mechanical motion and thus entering the tissues cells organisms. They hold great potential to revolutionize diagnosis treatment diseases by actively targeting lesion location, though there many new challenges that arise with decreasing size nanoscale. This review summarizes comments on state‐of‐the‐art artificial advantages limitations. It starts fabrication methods, including common physical vapor deposition colloidal chemistry followed locomotion characterization manipulation. Then, in vitro vivo biomedical applications introduced detail. The future prospects discussed at end.

Language: Английский

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Manipulating Nanoparticle Aggregates Regulates Receptor–Ligand Binding in Macrophages

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(13), P. 5769 - 5783

Published: March 11, 2022

The receptor–ligand interactions in cells are dynamically regulated by modulation of the ligand accessibility. In this study, we utilize size-tunable magnetic nanoparticle aggregates ordered at both nanometer and atomic scales. We flexibly anchor tunable sizes over cell-adhesive RGD (Arg-Gly-Asp)-active material surface while maintaining density dispersed ligands accessible to macrophages constant. Lowering dispersity increasing aggregate size constant facilitates binding integrin receptors ligands, which promotes adhesion macrophages. high dispersity, distant manipulation lift (which increases accessibility) stimulates available under augment macrophage adhesion-mediated pro-healing polarization vitro vivo. low control drop decreases repels away from aggregates, thereby suppressing adhesion, inflammatory polarization. Here, present "accessible dispersity" as a novel fundamental parameter that regulates binding, can be reversibly manipulated decreasing Limitless tuning dimensions morphology offer further insight into regulation host cells.

Language: Английский

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Cascade Catalytically Released Nitric Oxide‐Driven Nanomotor with Enhanced Penetration for Antibiofilm

Small, Journal Year: 2022, Volume and Issue: 18(52)

Published: Nov. 7, 2022

Nanodrugs are becoming increasingly important in the treatment of bacterial infection, but their low penetration ability to biofilm is still main challenge hindering therapeutic effect. Herein, nitric oxide (NO)-driven nanomotor based on L-arginine (L-Arg) and gold nanoparticles (AuNPs) loaded dendritic mesoporous silica (AG-DMSNs) fabricated. AG-DMSNs have characteristics cascade catalytic reaction, where glucose first catalyzed by asymmetrically distributed AuNPs with oxidase (GOx)- mimic property, which results unilateral production hydrogen peroxide (H2 O2 ). Then, L-Arg oxidized produced H2 release NO, leading self-propelled movement. It found that active movement promotes penetrate biofilm, thus achieving good clearance vitro. More importantly, can eliminate methicillin-resistant Staphylococcus aureus (MRSA) vivo without causing damage normal tissues. This provides a new platform for infections.

Language: Английский

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Polyoxometalate‐Nanozyme‐Integrated Nanomotors (POMotors) for Self‐Propulsion‐Promoted Synergistic Photothermal‐Catalytic Tumor Therapy

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(6)

Published: Dec. 20, 2023

Enzyme-powered nanomotors have demonstrated promising potential in biomedical applications, especially for catalytic tumor therapy, owing to their ability of self-propulsion and bio-catalysis. However, the fragility natural enzymes limits environmental adaptability also therapeutic efficacy catalysis-enabled therapy. Herein, polyoxometalate-nanozyme-based light-driven were designed synthesized targeted synergistic photothermal-catalytic In this construct, peroxidase-like activity P

Language: Английский

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