A Dihydroartemisinin‐Loaded Nanoreactor Motivates Anti‐Cancer Immunotherapy by Synergy‐Induced Ferroptosis to Activate Cgas/STING for Reprogramming of Macrophage

Advanced Healthcare Materials, Год журнала: 2023, Номер 12(28)

Опубликована: Авг. 11, 2023

Infiltration of tumor-associated macrophages (TAM) characterized by an M2 phenotype is overriding feature in malignant tumors. Reprogramming TAM the most cutting-edge strategy for cancer therapy. In present study, iron-based metal-organic framework (MOF) nanoreactor loaded with dihydroartemisinin (DHA) developed, which provides high uptake and retains their viability, thus effectively addressing inefficiency DHA at low concentrations. Impressively, DHA@MIL-101 can selectively accumulate tumor tissues remodel to M1 phenotype. The results RNA sequencing further suggest that this may regulate ferroptosis, a DNA damage signaling pathway TAM. Indeed, outcomes confirm triggers ferroptosis addition, findings reveal induced nanoreactors activates intracellular cGAS sensor, resulting binding STING IRF3 thereby up-regulating immunogenicity. contrast, blocking impairs DHA@MIL-101-induced activation phenotypic remodeling. Finally, it shown deploy anti-tumor immunotherapy through ferroptosis-mediated reprogramming. Taken together, immune efficacy achieved TAM's remodeling delivering iron ions into using nanoreactors, providing novel approach combining phytopharmaceuticals nanocarriers microenvironment.

Язык: Английский

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A Cancer Nanovaccine Based on an FeAl-Layered Double Hydroxide Framework for Reactive Oxygen Species-Augmented Metalloimmunotherapy

ACS Nano, Год журнала: 2024, Номер 18(11), С. 8143 - 8156

Опубликована: Март 4, 2024

The complexity and heterogeneity of individual tumors have hindered the efficacy existing therapeutic cancer vaccines, sparking intensive interest in development more effective situ vaccines. Herein, we introduce a nanovaccine for reactive oxygen species-augmented metalloimmunotherapy which FeAl-layered double hydroxide (LDH) is used as delivery vehicle with dihydroartemisinin (DHA) cargo. LDH framework acid-labile can be degraded tumor microenvironment, releasing iron ions, aluminum DHA. ions contribute to aggravated intratumoral oxidative stress injury by synergistic Fenton reaction DHA activation, causing apoptosis, ferroptosis, immunogenic cell death cells. subsequently released tumor-associated antigens adjuvant form generate robust long-term immune responses against recurrence metastasis. Moreover, Fe ion-enabled T1-weighted magnetic resonance imaging facilitate real-time therapy monitoring. This cancer-nanovaccine-mediated strategy has potential revolutionizing precision immunotherapy landscape.

Язык: Английский

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A pH and glutathione-responsive carbon monoxide-driven nano-herb delivery system for enhanced immunotherapy in colorectal cancer

Journal of Controlled Release, Год журнала: 2024, Номер 376, С. 659 - 677

Опубликована: Окт. 28, 2024

Язык: Английский

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Synthesis, characterization, and toxicity assessments of Silymarin-loaded Ni-Fe Metal-organic frameworks: Evidence from in vitro and in vivo evaluations

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 92, С. 105372 - 105372

Опубликована: Янв. 21, 2024

Язык: Английский

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Nanozyme-Based Strategies in Cancer Immunotherapy: Overcoming Resistance to Enhance Therapeutic Efficacy

Aging and Disease, Год журнала: 2025, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2025

Nanozymes, which are nanomaterials that replicate the catalytic activities of natural enzymes in biological systems, have recently demonstrated considerable potential improving cancer immunotherapy by altering tumor microenvironment. Nanozyme-driven immune responses represent an innovative therapeutic modality with high effectiveness and minimal side effects. These nanozymes activate system to specifically recognize destroy cells. Combined immunotherapeutic agents, can amplify anti-cancer integrating remodeling immunogenic cell death (ICD). This review offers a thorough discussion about various involved immunity, including those mimicking catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), oxidase (OXD). It also discusses challenges future directions for translating nanozyme platforms into clinical applications, enhancing susceptibility cells immunotherapy. Nanozyme-based strategies substantial oncology, offering new effective options management.

Язык: Английский

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Acidic Environment-Responsive Metal Organic Framework-Mediated Dihydroartemisinin Delivery for Triggering Production of Reactive Oxygen Species in Drug-Resistant Lung Cancer

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 3847 - 3859

Опубликована: Апрель 1, 2024

Background: Dihydroartemisinin (DHA) has emerged as a promising candidate for anticancer therapy. However, the application of DHA in clinics been hampered by several limitations including poor bioavailability, short circulation life, and low solubility, significantly restricting its therapeutic efficacy leading to notable side effects during treatment. Purpose: We present DHA-loaded zeolitic imidazolate framework-8 (D-ZIF) with controllable targeted release properties, enhanced antitumor while reducing potential effects. Methods: D-ZIF was prepared one-pot synthesis method using methylimidazole (MIM), Zn(NO 3 ) 2 • 6H O DHA. characterized physical chemical properties TEM, DLS, XRD, FT-IR, TG. measured drug loading efficiency cumulative different pH conditions. evaluated cytotoxicity on renal cell carcinoma (RCC786-O), glioma cells (U251), TAX-resistant human lung adenocarcinoma (A549-TAX) CCK8 vitro. explored possible mechanism Western blot. biocompatibility hemolysis vivo mice model TUNEL testing blood biomarker evaluations. Results: showed rhombic dodecahedral morphology size 129± 7.2 nm possessed noticeable encapsulation (72.9%). After 48 hours, released 70.0% loaded at 6.5, only 42.1% 7.4. The pH-triggered programmed behavior could enhance effect minimizing under normal physiological Compared free group 31.75% A549-TAX apoptosis, percentage apoptotic approximately 76.67% group. inhibited tumor growth inducing apoptosis through ROS production regulation Nrf2/HO-1 P38 MAPK signaling pathways. potent treating tumors high safety vivo. Conclusion: This pH-responsive targeting towards cells, thereby increasing concentration sites negligible Herein, holds great promise curing cancers minimal adverse Keywords: MOF, delivery, controlled release, cancer therapy

Язык: Английский

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Current status of controlled onco-therapies based on metal organic frameworks

RSC Advances, Год журнала: 2024, Номер 14(18), С. 12817 - 12828

Опубликована: Янв. 1, 2024

Most MOFs for controllable cancer treatment act as drug delivery vehicle and/or anti-cancer agent. Molecules with roles such chemotherapies, gases, peptides or nucleic acids can be loaded into that decompose in cells the TME to release its cargoes.

Язык: Английский

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Effects and mechanisms of N6-methyladenosine RNA methylation in environmental pollutant-induced carcinogenesis

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 277, С. 116372 - 116372

Опубликована: Апрель 25, 2024

Environmental pollution, including air plastic contamination, and heavy metal exposure, is a pressing global issue. This crisis contributes significantly to pollution-related diseases critical risk factor for chronic health conditions, cancer. Mounting evidence underscores the pivotal role of N6-methyladenosine (m

Язык: Английский

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Determining M2 macrophages content for the anti-tumor effects of metal-organic framework-encapsulated pazopanib nanoparticles in breast cancer

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 20, 2024

Abstract Pazopanib (PAZ), an oral multi-tyrosine kinase inhibitor, demonstrates promising cytostatic activities against various human cancers. However, its clinical utility is limited by substantial side effects and therapeutic resistance. We developed a nanoplatform capable of delivering PAZ for enhanced anti-breast cancer therapy. Nanometer-sized PAZ@Fe-MOF, compared to free PAZ, demonstrated increased anti-tumor in both syngeneic murine 4T1 xenograft MDA-MB-231 breast models. High-throughput single-cell RNA sequencing (scRNAseq) revealed that PAZ@Fe-MOF significantly reduced pro-tumorigenic M2-like macrophage populations at tumor sites suppressed M2-type signaling pathways, such as ATF6-TGFBR1-SMAD3, well chemokines including CCL17, CCL22, CCL24. reprogramed the inhibitory immune microenvironment curbed tumorigenicity blocking polarization M2 phenotype macrophages. This platform offers new strategy improving cytotoxicity It provides method evaluate immunological response cells PAZ-mediated treatment.

Язык: Английский

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2-Monoacylglycerol Mimetic Liposomes to Promote Intestinal Lymphatic Transport for Improving Oral Bioavailability of Dihydroartemisinin

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 5273 - 5295

Опубликована: Июнь 1, 2024

Purpose: Reducing the first-pass hepatic effect via intestinal lymphatic transport is an effective way to increase oral absorption of drugs. 2-Monoacylglycerol (2-MAG) as a primary digestive product dietary lipids triglyceride, can be assembled in chylomicrons and then transported from intestine into system. Herein, we propose biomimetic strategy report 2-MAG mimetic nanocarrier target system lipid pathway improve bioavailability. Methods: The liposomes were designed by covalently bonding serinol (SER) on surface named SER-LPs simulate structure 2-MAG. Dihydroartemisinin (DHA) was chosen model drug because its disadvantages such poor solubility high effect. endocytosis exocytosis mechanisms investigated Caco-2 cells cell monolayers. capacity evaluated ex vivo biodistribution pharmacokinetic experiments. Results: DHA loaded (SER-LPs-DHA) had particle size 70 nm desirable entrapment efficiency 93%. showed sustained release for simulated gastrointestinal environment. In vitro studies demonstrated that cellular uptake primarily relied caveolae- rather than clathrin-mediated preferred integrate chylomicron assembly process through endoplasmic reticulum/Golgi apparatus route. After administration, efficiently promoted accumulation mesenteric nodes. bioavailability 10.40-fold 1.17-fold larger free unmodified at same dose, respectively. Conclusion: improved efficient transport. These findings current study provide good alternative delivery drugs with metabolism. Keywords: transport, liposomes, metabolism, delivery, dihydroartemisinin

Язык: Английский

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