Heterostructural Nanoadjuvant CuSe/CoSe₂ for Potentiating Ferroptosis and Photoimmunotherapy through Intratumoral Blocked Lactate Efflux

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(13), P. 7205 - 7217

Published: March 23, 2023

The desirable curative effect in clinical immunotherapy has been challenging due to the immunosuppressive tumor microenvironment (TME) with high lactic acid (LA) metabolism solid tumors. Although targeting metabolic reprogramming of cells can restore survival and function immune TME, it is also plagued by insufficient immunogenicity. Herein, an activatable immunomodulatory nanoadjuvant CuSe/CoSe2@syrosingopine (CSC@Syro) constructed for simultaneously relieving TME boosting response. Specifically, CuSe/CoSe2 (CSC) exhibits TME-activated glutathione (GSH) depletion hydroxyl radical (•OH) generation potential ferroptosis. Meanwhile, remarkable photothermal conversion efficiency elevated photocatalytic ROS level both promote CSC heterostructures induce robust immunogenic cell death (ICD). Besides, loaded syrosingopine inhibitor achieves LA blockade cancer downregulating expression monocarboxylate transporter 4 (MCT4), which could sensitize ferroptosis intracellular milieu acidification neutralize acidic alleviate immunosuppression. Hence, advanced modulation confers potentiated infiltration ICD-stimulated T lymphocytes further reinforces antitumor therapy. In brief, CSC@Syro-mediated synergistic therapy elicit potent immunogenicity suppress proliferation metastasis effectually integrating regulation immunotherapy.

Language: Английский

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Circadian rhythms and cancers: the intrinsic links and therapeutic potentials

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 4, 2022

The circadian rhythm is an evolutionarily conserved time-keeping system that comprises a wide variety of processes including sleep-wake cycles, eating-fasting and activity-rest coordinating the behavior physiology all organs for whole-body homeostasis. Acute disruption may lead to transient discomfort, whereas long-term irregular will result in dysfunction organism, therefore increasing risks numerous diseases especially cancers. Indeed, both epidemiological experimental evidence has demonstrated intrinsic link between dysregulated cancer. Accordingly, rapidly understanding molecular mechanisms rhythms opening new options cancer therapy, possibly by modulating clock. In this review, we first describe general regulators their functions on addition, provide insights into underlying how several types (including sleep-wake, eating-fasting, activity-rest) can drive progression, which expand our development from clock perspective. Moreover, also summarize potential applications treatment, optional therapeutic strategy patients.

Language: Английский

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Dual‐Cascade Responsive Nanoparticles Enhance Pancreatic Cancer Therapy by Eliminating Tumor‐Resident Intracellular Bacteria

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(49)

Published: Sept. 9, 2022

The limited drug penetration and robust bacteria-mediated inactivation in pancreatic cancer result the failure of chemotherapy. To fight against these issues, a dual-cascade responsive nanoparticle (sNP@G/IR) that can sequentially trigger deep penetration, killing intratumor bacteria, controlled release chemo-drug, is reported. sNP@G/IR consists hyaluronic acid (HA) shell glutathione (GSH)-responsive polymer-core (NP@G/IR), encapsulates gemcitabine (Gem) photothermal agent (IR1048). polymer core, as an antibiotic alternative, tailored to exert optimal antibacterial activity selectivity. actively homes on tumor due CD44 targeting HA shell, which subsequently degraded by hyaluronidase extracellular matrix. resultant NP@G/IR decreased size reversed charge facilitates penetration. After cellular endocytosis, exposed guanidine kills intracellular bacteria through disrupting cell membranes. Intracellular GSH further triggers cargo. Thus, protected Gem eventually induces apoptosis. Under laser irradiation, hyperthermia IR1048 helps elimination tumors bacteria. Moreover, activates immune response, thereby reinforcing anticancer capacity. Therefore, this eliminates tumor-resident augments delivery efficacy, providing new avenue for improving therapy.

Language: Английский

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A Defect‐Engineered Nanozyme for Targeted NIR‐II Photothermal Immunotherapy of Cancer

Advanced Materials, Journal Year: 2022, Volume and Issue: 36(10)

Published: Oct. 10, 2022

Multienzyme-mimicking redox nanozymes, curated by defect engineering, in synergy with immunotherapy offer promising prospects for safe and efficient cancer therapy. However, the spatiotemporally precise immune response often gets challenged off-target adverse effects insufficient therapeutic response. Herein, a tumor cell membrane coated nanozyme (CMO-R@4T1) is reported combinational second near-infrared window (NIR-II) photothermal immunotherapy. CMO-R@4T1 consists of Cu-doped MoO

Language: Английский

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Tumor Microenvironment-Activable Manganese-Boosted Catalytic Immunotherapy Combined with PD-1 Checkpoint Blockade

ACS Nano, Journal Year: 2022, Volume and Issue: 16(12), P. 20400 - 20418

Published: Nov. 28, 2022

Immune checkpoint blockade (ICB) therapy has attracted widespread attention in cancer treatment. Due to the low immunogenicity and immune suppression state tumor microenvironment (TME), therapeutic effects are only moderate. Herein, a TME-activable manganese-boosted catalytic immunotherapy is designed for synergism with ICB kill tumors efficiently. The cell membrane (CM)-wrapping multienzyme-mimic manganese oxide (MnOx) nanozyme termed CM@Mn showed intrinsic peroxidase oxidase-like activities an acidic TME. These can generate toxic hydroxyl (•OH) superoxide radicals (•O2-) killing evoking immunogenic death (ICD). Furthermore, TME-responsive release of Mn2+ directly promotes dendritic maturation macrophage M1 repolarization, resulting reversal immunosuppressive TME into immune-activating environment. Additionally, hypoxia relief caused by catalase-like activity also contributes process reversal. Finally, robust tumor-specific T cell-mediated antitumor response occurs support PD-1 blockade. proliferation primary metastatic was inhibited, long-term memory effect induced. strategy outlined here may serve as promising candidate tumor-integrated

Language: Английский

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Nanoparticle‐Based Photothermal Therapy for Breast Cancer Noninvasive Treatment

Advanced Materials, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 10, 2023

Rapid advancements in materials science and nanotechnology, intertwined with oncology, have positioned photothermal therapy (PTT) as a promising noninvasive treatment strategy for cancer. The breast's superficial anatomical location aesthetic significance render breast cancer particularly pertinent candidate the clinical application of PTT following melanoma. This review comprehensively explores research conducted on various types nanoparticles employed elaborates their specific roles mechanisms action. integration existing therapies is scrutinized, underscoring its potential synergistic outcomes. Additionally, underlying consequential modifications to tumor microenvironment after are elaborated from medical perspective. Future directions suggested, an emphasis development integrative platforms that combine multiple therapeutic approaches optimization nanoparticle synthesis enhanced efficacy. goal push boundaries toward comprehensive, clinically applicable

Language: Английский

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Glutathione‐Depleting Organic Metal Adjuvants for Effective NIR‐II Photothermal Immunotherapy

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(21)

Published: March 31, 2022

Although photothermal immunotherapy (PTI) is a compelling strategy for tumor therapy, the development of promising agents to overcome insufficient immunogenicity cells and poor immune response encountered in PTI still challenging. Herein, commercial small-molecule-based organic metal adjuvants (OMAs) are presented, with second near-infrared photoacoustic properties as well ability perturb redox homeostasis potentiate responsiveness. OMAs, assembled from charge-transfer complexes characterized by broad substrate scope, high accessibility, flexibly tuned optical properties, demonstrate strong phototherapeutic adjuvant abilities via depletion glutathione cysteine, subsequently elicit systemic immunity evoking immunogenic cell death, promoting dendritic maturation, increasing T infiltration. Furthermore, programmed death protein 1 antibody can be employed synergize OMAs suppress evasion ultimately improve treatment outcomes. This study unlocks new paradigms provide versatile OMA-based scaffold future practical applications.

Language: Английский

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Antitumor Applications of Photothermal Agents and Photothermal Synergistic Therapies

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(14), P. 7909 - 7909

Published: July 18, 2022

As a new tumor treatment strategy, photothermal therapy (PTT) has the advantages of accuracy, ease administration, high efficiency and low side effects. Photothermal transduction agents (PTAs) are key factor which play an important role in PTT. The mechanism PTT is discussed detail. conversion (PCE) can be improved by increasing light absorption reducing scattering agents. Additionally, non-radiative relaxation path attenuation also promote energy to obtain higher value terms PCE. structure characteristics various kinds PTAs (metal materials, carbon-based nanomaterials, two-dimensional organic materials) were compared analyzed. This paper reviews antitumor applications synergistic therapies, including combined with immunotherapy, chemotherapy, photodynamic therapy. review proposes that these development therapies have great potential application treatment.

Language: Английский

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Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies

Redox Biology, Journal Year: 2023, Volume and Issue: 59, P. 102601 - 102601

Published: Jan. 7, 2023

Hydrogen sulfide (H2S) is an important signaling molecule in colorectal cancer (CRC). It produced the colon by catalytic synthesis of colonocytes' enzymatic systems and release intestinal microbes, oxidatively metabolized mitochondria. Both endogenous H2S colonic epithelial cells exogenous lumen contribute to onset progression CRC. The up-regulation synthetases thought be cause elevated levels CRC cells. Different diagnostic probes combination therapies, as well tumor treatment approaches through modulation, have been developed recent years become active area investigation for diagnosis In this review, we focus on specific mechanisms production oxidative metabolism function occurrence, progression, diagnosis, We also discuss present challenges provide insights into future research burgeoning field.

Language: Английский

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Gas‐Mediated Tumor Energy Remodeling for Sensitizing Mild Photothermal Therapy

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(27)

Published: May 4, 2023

Abstract The metabolic reprogramming of tumors requires high levels adenosine triphosphate (ATP) to maintain therapeutic resistance, posing a major challenge for photothermal therapy (PTT). Although raising the temperature helps in tumor ablation, it frequently leads severe side effects. Therefore, improving response and promoting healing are critical considerations development PTT. Here, we proposed gas‐mediated energy remodeling strategy improve mild PTT efficacy while minimizing In proof‐of‐concept study, Food Drug Administration (FDA)‐approved drug‐based hydrogen sulfide (H 2 S) donor was developed provide sustained supply H S sites, serving as an adjuvant This approach proved be highly effective disrupting mitochondrial respiratory chain, inhibiting ATP generation, reducing overexpression heat shock protein 90 (HSP90), which ultimately amplified outcome. With ability reverse thermotolerance, this delivered greatly potent antitumor response, achieving complete ablation single treatment harm healthy tissues. Thus, holds great promise universal solution overcoming limitations may serve valuable paradigm future clinical translation nanoagents.

Language: Английский

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