Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy

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

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Bioorthogonal Guided Activation of cGAS‐STING by AIE Photosensitizer Nanoparticles for Targeted Tumor Therapy and Imaging

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(52)

Published: Sept. 5, 2023

Abstract Photodynamic therapy (PDT) and photothermal (PTT) leverage reactive oxygen species (ROS) control local hyperthermia by photosensitizer to perturb intracellular redox equilibrium, inducing DNA damage in both mitochondria nucleus, activating the cGAS‐STING pathway, ultimately eliciting antitumor immune responses. However, current photosensitizers are encumbered limitations such as suboptimal tumor targeting, aggregation‐caused quenching (ACQ), restricted excitation emission wavelengths. Here, this work designs novel nanoparticles based on aggregation‐induced (AIE) (BODTPE) for targeted near‐infrared II fluorescence imaging (NIR‐II FLI) with enhanced PDT/PTT effects. BODTPE is employed a monomer, dibenzocyclooctyne (DBCO)‐PEG 2k ‐amine serving an end‐capping polymer, synthesize BODTPE‐containing polymer (DBD). Further, through self‐assembly, DBD mPEG‐DSPE combined form (NP‐DBD). Notably, DBCO surface of NP‐DBD can react azide groups cancer cells pretreated Ac 4 ManNAz copper‐free click reaction. This innovative formulation led accumulation within sites, phenomenon convincingly demonstrated murine models subjected N ‐azidoacetylmannosamine‐tetraacylated (Ac ManNAz) pretreatment. Significantly, exhibits multifaceted effect encompassing PDT/PTT/NIR‐II FLI upon 808 nm laser irradiation, thereby better culminating compelling inhibition augmented robust modulation.

Language: Английский

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Reduction of Platinum(IV) Prodrug Hemoglobin Nanoparticles with Deeply Penetrating Ultrasound Radiation for Tumor‐Targeted Therapeutically Enhanced Anticancer Therapy

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(22)

Published: March 24, 2023

The development of PtIV prodrugs that are reduced into the therapeutically active PtII species within tumor microenvironment has received much research interest. In order to provide spatial and temporal control over treatment, there is a high demand for compounds could be selectively activated upon irradiation. Despite recent progress, majority complexes excited with ultraviolet or blue light, limiting use such superficial application. To overcome this limitation, herein, first example prodrug nanoparticles deeply penetrating ultrasound radiation reported, enabling treatment deep-seated large tumors. were found accumulate inside mouse colon carcinoma intravenous injection able eradicate exposure radiation.

Language: Английский

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Simultaneous Activation of Pyroptosis and cGAS‐STING Pathway with Epigenetic/ Photodynamic Nanotheranostic for Enhanced Tumor Photoimmunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(7)

Published: Oct. 5, 2023

Promoting innate immunity through pyroptosis induction or the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway activation has emerged as a potent approach to counteract immunosuppressive tumor microenvironment and elicit systemic antitumor immunity. However, current inducers STING agonists often suffer from limitations including instability, unpredictable side effects, inadequate intracellular expression gasdermin STING. Here, tumor-specific nanotheranostic platform that combines photodynamic therapy (PDT) with epigenetic simultaneously activate cGAS-STING in light-controlled manner is constructed. This involves development oxidation-sensitive nanoparticles (NP1) loaded photosensitizer TBE, along decitabine nanomicelles (NP2). NP2 enables restoration E (GSDME) expression, while NP1-mediated PDT facilitates release DNA fragments damaged mitochondria potentiate pathway, promotes caspase-3 cleave upregulated GSDME into pore-forming GSDME-N terminal. Subsequently, released inflammatory cytokines facilitate maturation antigen-presentation cells, triggering T cell-mediated Overall, this study presents an elaborate strategy for simultaneous photoactivation enabling targeted photoimmunotherapy immunotolerant tumors. innovative holds significant promise overcoming associated existing therapeutic modalities represents valuable avenue future clinical applications.

Language: Английский

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A STING pathway-activatable contrast agent for MRI-guided tumor immunoferroptosis synergistic therapy

Biomaterials, Journal Year: 2023, Volume and Issue: 302, P. 122300 - 122300

Published: Aug. 29, 2023

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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Metal‐based smart nanosystems in cancer immunotherapy

Exploration, Journal Year: 2024, Volume and Issue: 4(6)

Published: March 22, 2024

Abstract Metals are an emerging topic in cancer immunotherapy that have shown great potential modulating immunity cycle and promoting antitumor by activating the intrinsic immunostimulatory mechanisms which been identified recent years. The main challenge of metal‐assisted lies fact free metals as ion forms easily cleared during circulation, even cause systemic metal toxicity due to off‐target effects. With rapid development nanomedicine, metal‐based smart nanosystems (MSNs) with unique controllable structure become one most promising delivery carriers solve issue, owing their various endogenous/external stimuli‐responsiveness release ions for metalloimmunotherapy. In this review, state‐of‐the‐art research progress metal‐related is comprehensively summarized. First, mainstream MSNs‐assisted will be delineated. immunological effects certain categorization MSNs different characters compositions then provided, followed representative exemplar applications treatment, synergistic combination immunotherapy. Finally, we conclude review a summary remaining challenges associated provide authors' perspective on further advances.

Language: Английский

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Nanomaterial-encapsulated STING agonists for immune modulation in cancer therapy

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 7, 2024

Abstract The cGAS-STING signaling pathway has emerged as a critical mediator of innate immune responses, playing crucial role in improving antitumor immunity through effector responses. Targeting the holds promise for overcoming immunosuppressive tumor microenvironments (TME) and promoting effective elimination. However, systemic administration current STING agonists faces challenges related to low bioavailability potential adverse effects, thus limiting their clinical applicability. Recently, nanotechnology-based strategies have been developed modulate TMEs robust immunotherapeutic encapsulation delivery within nanoparticles (STING-NPs) present an attractive avenue immunotherapy. This review explores range designed encapsulate agonists, highlighting benefits, including favorable biocompatibility, improved penetration, efficient intracellular agonists. also summarizes immunomodulatory impacts STING-NPs on TME, enhanced secretion pro-inflammatory cytokines chemokines, dendritic cell activation, cytotoxic T priming, macrophage re-education, vasculature normalization. Furthermore, offers insights into co-delivered nanoplatforms involving alongside agents such chemotherapeutic compounds, checkpoint inhibitors, antigen peptides, other adjuvants. These platforms demonstrate remarkable versatility inducing immunogenic responses ultimately amplifying

Language: Английский

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The Role of Oxidative Stress in Tumorigenesis and Progression

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 441 - 441

Published: March 2, 2024

Oxidative stress refers to the imbalance between production of reactive oxygen species (ROS) and endogenous antioxidant defense system. Its involvement in cell senescence, apoptosis, series diseases has been demonstrated. Advances carcinogenic research have revealed oxidative as a pivotal pathophysiological pathway tumorigenesis be involved lung cancer, glioma, hepatocellular carcinoma, leukemia, so on. This review combs effects on each phase fate determination, three features are discussed. takes part processes ranging from tumor death via pathways like mitochondrial stress, endoplasmic reticulum ferroptosis. It can affect by engaging complex relationships death, cancer. The influence progression is multi-stage interlaced process that includes two aspects promotion inhibition, with mitochondria core regulation. A deeper more comprehensive understanding conducive exploring therapies.

Language: Английский

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Circulating immunotherapy strategy based on pyroptosis and STING pathway: Mn-loaded paclitaxel prodrug nanoplatform against tumor progression and metastasis

Biomaterials, Journal Year: 2024, Volume and Issue: 306, P. 122472 - 122472

Published: Jan. 23, 2024

Language: Английский

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