Mecheliolide elicits ROS-mediated ERS driven immunogenic cell death in hepatocellular carcinoma

Redox Biology, Год журнала: 2022, Номер 54, С. 102351 - 102351

Опубликована: Май 28, 2022

The nonnegligible reason for the poor prognosis of hepatocellular carcinoma (HCC) is resistance to conventional chemotherapy. Immunogenic cell death (ICD) a rare immunostimulatory form that can reengage tumor-specific immune system. ICD improve clinical outcomes chemotherapeutics by promoting long-term cancer immunity. discovery potential inducers emerging as promising direction. In present study, micheliolide (MCL), natural guaianolide sesquiterpene lactone, was screened out virtual screening strategies, identified an inhibitor thioredoxin reductase (TrxR) and evaluated have high induce ICD. Here, we showed MCL induced ICD-associated DAMPs (damage-associated molecular patterns, such CRT exposure, ATP secretion HMGB1 release). significantly triggered regression established tumors in immunocompetent mouse vaccine model, (DCs maturation, stimulation CD4+, CD8+ T-cells responses) vivo. Mechanistically, found magnitude effects upon exposure HCC cells dependent on generation reactive oxygen species (ROS)-mediated endoplasmic reticulum stress (ERS). addition, suppression ROS normalized MCL-induced ERS, contrast, downregulation TrxR synergized with ERS driven MCL. We also systematically detected H2O2 using Hyper7 sensors exposed Notably, inhibited development organoids. Collectively, our results reveal association between inhibitors ICD, presenting valuable insights into MCL-activated cells.

Язык: Английский

---

Advancement of cancer immunotherapy using nanoparticles-based nanomedicine

Seminars in Cancer Biology, Год журнала: 2022, Номер 86, С. 624 - 644

Опубликована: Апрель 1, 2022

Язык: Английский

---

Extracellular‐Vesicle‐Based Drug Delivery Systems for Enhanced Antitumor Therapies through Modulating the Cancer‐Immunity Cycle

Advanced Materials, Год журнала: 2022, Номер 34(52)

Опубликована: Июнь 21, 2022

Although immunotherapy harnessing activity of the immune system against tumors has made great progress, treatment efficacy remains limited in most cancers. Current anticancer is primarily based on T-cell-mediated cellular immunity, which highly relies efficiency triggering cancer-immunity cycle, namely, tumor antigen release, presentation by presenting cells, T cell activation, recruitment and infiltration cells into tumors, recognition killing cells. Unfortunately, these immunotherapies are restricted inefficient drug delivery acting only a single step cycle. Due to high biocompatibility, low immunogenicity, intrinsic targeting, easy chemical genetic manipulation, extracellular vesicle (EV)-based systems widely used amplify responses serving as an integrated platform for multiple drugs or therapeutic strategies synergistically activate several steps This review summarizes various mechanisms related affecting cycle disorders. Meanwhile, preparation application EV-based modulating introduced, especially improvement tumors. Finally, opportunities challenges translational clinical applications briefly discussed.

Язык: Английский

---

Nano delivery of simvastatin targets liver sinusoidal endothelial cells to remodel tumor microenvironment for hepatocellular carcinoma

Journal of Nanobiotechnology, Год журнала: 2022, Номер 20(1)

Опубликована: Янв. 4, 2022

Abstract Background Hepatocellular carcinoma (HCC) developed in fibrotic liver does not respond well to immunotherapy, mainly due the stromal microenvironment and fibrosis-related immunosuppressive factors. The characteristic of sinusoidal endothelial cells (LSECs) contributing fibrosis orchestrating immune response is responsible for refractory targeted therapy or immunotherapy HCC. We aim seek a new strategy HCC treatment based on an old drug simvastatin which shows protecting effect LSEC. Method features LSECs mouse model human patients were identified by immunofluorescence scanning electron microscopy. hepatic stellate (HSCs) was examined immunoblotting, quantitative RT-PCR RNA-seq. LSEC-targeted delivery designed using nanotechnology. anti-HCC toxicity nano-drug evaluated both intra-hepatic hemi-splenic inoculated model. Results LSEC capillarization associated with progression poor survival murine patients. further found restores quiescence activated (aHSCs) via stimulation KLF2-NO signaling LSECs, up-regulates expression CXCL16 LSECs. In intrahepatic model, nano-delivery only alleviates regress microenvironment, but also recruits natural killer T (NKT) through suppress tumor progression. Together anti-programmed death-1-ligand-1 (anti-PD-L1) antibody, targeted-delivery achieves improved therapeutic advanced-stage Conclusions These findings reveal immune-based mechanism remodeling therefore providing novel treating Graphical

Язык: Английский

---

Enhancement of anti-PD-1/PD-L1 immunotherapy for osteosarcoma using an intelligent autophagy-controlling metal organic framework

Biomaterials, Год журнала: 2022, Номер 282, С. 121407 - 121407

Опубликована: Фев. 17, 2022

Язык: Английский

---

Chemotherapeutic and targeted drugs-induced immunogenic cell death in cancer models and antitumor therapy: An update review

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Апрель 21, 2023

As traditional strategies for cancer treatment, some chemotherapy agents, such as doxorubicin, oxaliplatin, cyclophosphamide, bortezomib, and paclitaxel exert their anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells. ICD induces immunity through release of, or exposure to, damage-related molecular patterns (DAMPs), including high mobility group box 1 (HMGB1), calreticulin, adenosine triphosphate, heat shock proteins. This leads to activation tumor-specific immune responses, which can act in combination with the direct killing functions drugs on cells further improve curative effects. In this review, we highlight mechanisms underlying ICD, those several chemotherapeutic DAMPs exposed during activate system, well discussing prospects application potential role immunotherapy, aim providing valuable inspiration future development chemoimmunotherapy.

Язык: Английский

---

Nano Delivery of Chemotherapeutic ICD Inducers for Tumor Immunotherapy

Small Methods, Год журнала: 2023, Номер 7(5)

Опубликована: Янв. 5, 2023

Immunogenic cell death (ICD, also known as immunogenic apoptosis) of malignant cells is confirmed to activate the host immune system prevent, control, and eliminate tumors. Recently, a range chemotherapeutic drugs have been repurposed ICD inducers applied for tumor immunotherapy. However, several hurdles widespread application remain, namely poor water solubility, short blood circulation, non-specific tissue distribution, severe toxicity. Recent advances in nanotechnology pharmaceutical formulation foster development nano drug delivery systems tackle aforementioned expedite safe, effective, specific delivery. This review will describe barriers chemical highlight recent nanoformulations these

Язык: Английский

---

Exploring pharmacological active ingredients of traditional Chinese medicine by pharmacotranscriptomic map in ITCM

Briefings in Bioinformatics, Год журнала: 2023, Номер 24(2)

Опубликована: Янв. 31, 2023

With the emergence of high-throughput technologies, computational screening based on gene expression profiles has become one most effective methods for drug discovery. More importantly, profile-based approaches remarkably enhance novel drug-disease pair discovery without relying drug- or disease-specific prior knowledge, which been widely used in modern medicine. However, systematic active ingredients traditional Chinese medicine (TCM) scarcely performed due to inadequate pharmacotranscriptomic data. Here, we develop largest-to-date online TCM ingredients-based platform integrated (ITCM) ingredients. First, unified experiments and constructed largest data repository 496 representative ingredients, was five times larger than previous built by our team. The transcriptome-based multi-scale analysis also elucidate their mechanism. Then, developed six state-of-art signature search screen determine optimal size all methods. Moreover, them into a strategy, TCM-Query, identify potential special disease. In addition, comprehensively collected TCM-related resource literature mining. Finally, applied ITCM an ingredient bavachinin, two diseases, including prostate cancer COVID-19, demonstrate power aimed explore boost studies pharmacological action is available at http://itcm.biotcm.net.

Язык: Английский

---

m6A-regulated tumor glycolysis: new advances in epigenetics and metabolism

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Авг. 15, 2023

Abstract Glycolytic reprogramming is one of the most important features cancer and plays an integral role in progression cancer. In cells, changes glucose metabolism meet needs self-proliferation, angiogenesis lymphangiogenesis, metastasis, also affect immune escape, prognosis evaluation therapeutic effect The n6-methyladenosine (m6A) modification RNA widespread eukaryotic cells. Dynamic reversible m6A modifications are widely involved regulation stem cell renewal differentiation, tumor therapy resistance, microenvironment, metabolism. Lately, more evidences show that can glycolysis process tumors a variety ways to regulate biological behavior tumors. this review, we discussed genesis development, elaborated detail profound impact on different by regulating glycolysis. We believe modified has great significance potential for treatment.

Язык: Английский

---

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

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(13), С. 8991 - 9003

Опубликована: Март 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.

Язык: Английский

---