Novel plant-derived exosome-like nanovesicles from Catharanthus roseus: preparation, characterization, and immunostimulatory effect via TNF-α/NF-κB/PU.1 axis

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 20, 2023

Abstract Background Plant-derived exosomes-like nanovesicles (PDENs) have been found to be advantageous in disease treatment and drug delivery, but research on their biogenesis, compositional analysis, key marker proteins is still its infancy, which limits the standardized production of PDENs. Efficient preparation PDENs continues a major challenge. Results Novel PDENs-based chemotherapeutic immune modulators, Catharanthus roseus (L.) Don leaves-derived exosome-like (CLDENs) were isolated from apoplastic fluid. CLDENs membrane structured vesicles with particle size 75.51 ± 10.19 nm surface charge −21.8 mV. exhibited excellent stability, tolerating multiple enzymatic digestions, resisting extreme pH environments, remaining stable gastrointestinal simulating Biodistribution experiments showed that could internalized by cells, targeted at organs after intraperitoneal injection. The lipidomic analysis revealed CLDENs’ special lipid composition, contained 36.5% ether-phospholipids. Differential proteomics supported origin multivesicular bodies, six identified for first time. 60 ~ 240 μg/ml promoted polarization phagocytosis macrophages as well lymphocyte proliferation vitro. Administration 20 mg/kg alleviated white blood cell reduction bone marrow cycle arrest immunosuppressive mice induced cyclophosphamide. strongly stimulated secretion TNF-α, activated NF-κB signal pathway increased expression hematopoietic function-related transcription factor PU.1 both vitro vivo. To ensure steady supply CLDENs, plant culture systems C. established provide CLDENs-like had similar physical properties biological activities. Gram-level successfully obtained medium, yield was three times high original. Conclusions Our supports use nano-biomaterial stability biocompatibility, post-chemotherapy adjuvant therapy applications. Graphical

Language: Английский

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A bioinformatics analysis, pre-clinical and clinical conception of autophagy in pancreatic cancer: Complexity and simplicity in crosstalk

Pharmacological Research, Journal Year: 2023, Volume and Issue: 194, P. 106822 - 106822

Published: June 17, 2023

Pancreatic cancer (PC) is a serious gastrointestinal tract disease for which the 5-year survival rate less than 10%, even in developed countries such as USA. The genomic profile alterations and dysregulated biological mechanisms commonly occur PC. Macroautophagy/autophagy cell death process that maintained at basal level physiological conditions, whereas its often changes during tumorigenesis. function of autophagy human cancers dual can be oncogenic onco-suppressor. Autophagy potent controller tumorigenesis supportive PC escalates growth cells suppression mediate death. also determines metastasis cells, it control EMT affecting migration. Moreover, starvation hypoxia stimulate glycolysis, glycolysis induction mediated by enhancing Furthermore, protective stimulates drug resistance gemcitabine inhibition enhance radiosensitivity. degrade MHC-I to immune evasion regulates polarization macrophages tumor microenvironment. Modulation activity provided silibinin, ursolic acid, chrysin huaier treatment Non-coding RNAs are controllers improve therapy response patients. mitophagy shows dysregulation PC, proliferation cells. Therefore, bioinformatics analysis demonstrates autophagy-related proteins genes biomarkers.

Language: Английский

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The promising role of tumor-associated macrophages in the treatment of cancer

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 73, P. 101041 - 101041

Published: Jan. 3, 2024

Language: Английский

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Molecular profile of metastasis, cell plasticity and EMT in pancreatic cancer: a pre-clinical connection to aggressiveness and drug resistance

Cancer and Metastasis Reviews, Journal Year: 2023, Volume and Issue: 43(1), P. 29 - 53

Published: July 15, 2023

Language: Английский

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Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 2, 2024

Abstract Metastasis remains a pivotal characteristic of cancer and is the primary contributor to cancer-associated mortality. Despite its significance, mechanisms governing metastasis are not fully elucidated. Contemporary findings in domain biology have shed light on molecular aspects this intricate process. Tumor cells undergoing invasion engage with other cellular entities proteins en route their destination. Insights into these engagements enhanced our comprehension principles directing movement adaptability metastatic cells. The tumor microenvironment plays role facilitating proliferation by enabling navigate through stromal barriers. Such attributes influenced genetic epigenetic changes occurring surrounding milieu. A profound understanding process’s biological indispensable for devising efficacious therapeutic strategies. This review delves recent developments concerning metastasis-associated genes, important signaling pathways, microenvironment, metabolic processes, peripheral immunity, mechanical forces metastasis. In addition, we combine advances particular emphasis prospect developing effective interventions including most popular immunotherapies nanotechnology combat We also identified limitations current research metastasis, encompassing drug resistance, restricted animal models, inadequate biomarkers early detection methods, as well heterogeneity among others. It anticipated that comprehensive will significantly contribute advancement research.

Language: Английский

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Research status and challenges of plant-derived exosome-like nanoparticles

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 174, P. 116543 - 116543

Published: April 11, 2024

In recent years, there has been an increasing number of related studies on exosomes. Most have focused exosomes derived from mammals, confirming the important role that play in cell communication. Plants, as a natural ingredient, plant-derived confirmed to similar structures and functions mammalian-derived Plant-derived exosome-like nanoparticles (PELNs) are lipid bilayer membrane nanovesicles containing bioactive constituents such miRNA, mRNA, protein, lipids obtained plant cells, can participate intercellular communication mediate transboundary communication, high bioavailability low immunogenicity, relatively safe, shown maintaining homeostasis preventing, treating variety diseases. this review, we describe biogenesis, isolation purification methods, structural composition, stability, safety, function PELNs challenges. The anti-inflammatory, antioxidant, antitumor drug delivery mainly described, status research exosome Chinese herbal medicines is outlined. Overall, summarized importance latest results field provided theoretical basis for future clinical application PELNs.

Language: Английский

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Cancer-derived exosomes as novel biomarkers in metastatic gastrointestinal cancer

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 1, 2024

Abstract Gastrointestinal cancer (GIC) is the most prevalent and highly metastatic malignant tumor has a significant impact on mortality rates. Nevertheless, swift advancement of contemporary technology not seamlessly aligned with evolution detection methodologies, resulting in deficit innovative efficient clinical assays for GIC. Given that exosomes are preferentially released by myriad cellular entities, predominantly originating from neoplastic cells, this confers composition enriched cancer-specific constituents. Furthermore, exhibit ubiquitous presence across diverse biological fluids, endowing them inherent advantages non-invasiveness, real-time monitoring, specificity. The unparalleled render as an ideal liquid biopsy biomarker early diagnosis, prognosticating potential development GIC metastasis. In review, we summarized latest research progress possible targets cancer-derived (CDEs) emphasis mechanisms exosome promoting metastasis, highlighting roles CDEs treatment

Language: Английский

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Extracellular vesicles in tumor immunity: mechanisms and novel insights

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 14, 2025

Extracellular vesicles (EVs), nanoscale secreted by cells, have attracted considerable attention in recent years due to their role tumor immunomodulation. These facilitate intercellular communication transporting proteins, nucleic acids, and other biologically active substances, they exhibit a dual development immune evasion mechanisms. Specifically, EVs can assist cells evading surveillance attack impairing cell function or modulating immunosuppressive pathways, thereby promoting progression metastasis. Conversely, also transport release immunomodulatory factors that stimulate the activation regulation of system, enhancing body's capacity combat malignant diseases. This functionality presents promising avenues targets for immunotherapy. By examining biological characteristics influence on immunity, novel therapeutic strategies be developed improve efficacy relevance cancer treatment. review delineates complex immunomodulation explores potential implications approaches, aiming establish theoretical foundation provide practical insights advancement future EVs-based immunotherapy strategies.

Language: Английский

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Molecular and metabolic regulation of immunosuppression in metastatic pancreatic ductal adenocarcinoma

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: July 24, 2023

Immunosuppression is a hallmark of pancreatic ductal adenocarcinoma (PDAC), contributing to early metastasis and poor patient survival. Compared the localized tumors, current standard-of-care therapies have failed improve survival patients with metastatic PDAC, that necessecitates exploration novel therapeutic approaches. While immunotherapies such as immune checkpoint blockade (ICB) vaccines emerged promising treatment modalities in certain cancers, limited responses been achieved PDAC. Therefore, specific mechanisms regulating response immunotherapy must be explored. The immunosuppressive microenvironment driven by oncogenic mutations, tumor secretome, non-coding RNAs, microbiome persists throughout PDAC progression, allowing neoplastic cells grow locally metastasize distantly. escaping host surveillance are unique molecular, immunological, metabolic characteristics. Following chemokine exosomal guidance, these organ-specific pre-metastatic niches (PMNs) constituted local resident cells, stromal fibroblasts, suppressive metastasis-associated macrophages, neutrophils, myeloid-derived suppressor cells. differs from primary tumors cell composition, functionality, metabolism. Thus far, multiple molecular pathways, distinct identified dampen effector functions, confounding This review describes major immunoregulatory pathways contribute progression limit outcomes Overall, we highlight vulnerabilities attributable factors discuss whether targeting immunological "hot spots" could immunotherapies.

Language: Английский

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Exosomes in the tumor microenvironment: Promoting cancer progression

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 6, 2022

Exosomes, which are extracellular vesicles produced by endosomes, important performers of intercellular communication functions. For more than three decades, there has been a growing awareness exosomes as the contents tumor microenvironment and their intimate connection to development cancer. The composition, generation, uptake well roles in metastasis, angiogenesis, immunosuppression discussed this paper. In order stop progression cancer, it is crucial find new diagnostic biomarkers therapeutic targets for disease. Knowing biological characteristics functions helps endeavor.

Language: Английский

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