Current Strategies for Exosome Cargo Loading and Targeting Delivery

Cells, Journal Year: 2023, Volume and Issue: 12(10), P. 1416 - 1416

Published: May 17, 2023

Extracellular vesicles (EVs) such as ectosomes and exosomes have gained attention promising natural carriers for drug delivery. Exosomes, which range from 30 to 100 nm in diameter, possess a lipid bilayer are secreted by various cells. Due their high biocompatibility, stability, low immunogenicity, favored cargo carriers. The membrane of also offers protection against degradation, making them desirable candidate However, loading into remains be challenge. Despite strategies incubation, electroporation, sonication, extrusion, freeze–thaw cycling, transfection that been developed facilitate loading, inadequate efficiency still persists. This review an overview current delivery using summarizes recent approaches small-molecule, nucleic acid, protein drugs exosomes. With insights these studies, we provide ideas more efficient effective molecules

Language: Английский

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CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Oct. 20, 2022

Ferroptosis is a novel form of iron-dependent cell death and participates in the malignant progression glioblastoma (GBM). Although circular RNAs (circRNAs) are found to play key roles ferroptosis via several mechanisms, including regulating iron metabolism, glutathione lipid peroxidation mitochondrial-related proteins, there many circRNAs need be found, they may become new molecular treatment target GBM.The expression levels circLRFN5, PRRX2 GCH1 were detected by qPCR, western blotting, immunohistochemistry. Lentiviral-based infections used overexpress or knockdown these molecules glioma stem cells (GSCs). The biological functions on GSCs MTS (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium), 5-ethynyl-20-deoxyuridine (EdU) incorporation assay, transwell, neurosphere formation assays, Extreme Limiting Dilution Analysis (ELDA) xenograft experiments. content was BODIPY 581/591 C11 (GSH) assay malondialdehyde (MDA) assay. mechanisms among studied RNA immunoprecipitation pull-down ubiquitination dual-luciferase reporter chromatin assay.We circRNA circLRFN5 downregulated GBM associated with patients' poor prognosis. CircLRFN5 overexpression inhibits viabilities, proliferation, neurospheres formation, stemness tumorigenesis inducing ferroptosis. Mechanistically, binds protein promotes its degradation ubiquitin-mediated proteasomal pathway. can transcriptionally upregulate GSCs, which suppressor generating antioxidant tetrahydrobiopterin (BH4).Our study as tumor-suppressive identified role GBM. potential biomarker for therapies ferroptosis-dependent therapy

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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New insight into circRNAs: characterization, strategies, and biomedical applications

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Oct. 12, 2023

Abstract Circular RNAs (circRNAs) are a class of covalently closed, endogenous ncRNAs. Most circRNAs derived from exonic or intronic sequences by precursor RNA back-splicing. Advanced high-throughput sequencing and experimental technologies have enabled the extensive identification characterization circRNAs, such as novel types biogenesis, tissue-specific cell-specific expression patterns, epigenetic regulation, translation potential, localization metabolism. Increasing evidence has revealed that participate in diverse cellular processes, their dysregulation is involved pathogenesis various diseases, particularly cancer. In this review, we systematically discuss databases, challenges for circRNA discovery, new insight into strategies used studies biomedical applications. Although recent advanced understanding knowledge approaches annotation, functional applications continuously needed to provide insights circRNAs. The emergence circRNA-based protein strategy will be promising direction field biomedicine.

Language: Английский

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Optical Nanobiosensor Based on Surface-Enhanced Raman Spectroscopy and Catalytic Hairpin Assembly for Early-Stage Lung Cancer Detection via Blood Circular RNA

ACS Sensors, Journal Year: 2024, Volume and Issue: 9(4), P. 2020 - 2030

Published: April 11, 2024

Lung cancer has become the leading cause of cancer-related deaths globally. However, early detection lung remains challenging, resulting in poor outcomes for patients. Herein, we developed an optical biosensor integrating surface-enhanced Raman spectroscopy (SERS) with a catalyzed hairpin assembly (CHA) to detect circular RNA (circRNA) associated tumor formation and progression (circSATB2). The signals reporter were considerably enhanced by generating abundant SERS "hot spots" core–shell nanoprobe 2D substrate calibration capabilities. This approach enabled sensitive (limit detection: 0.766 fM) reliable quantitative target circRNA. Further, used circRNA human serum samples, revealing that patients had higher concentrations than healthy subjects. Moreover, characterized unique concentration profiles stages (IA IB) subtypes (IA1, IA2, IA3) cancer. These results demonstrate potential proposed sensing nanoplatform as liquid biopsy prognostic tool screening

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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Mechanisms and therapeutic implications of gene expression regulation by circRNA-protein interactions in cancer

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 17, 2025

Circular RNAs (circRNAs) have garnered substantial attention due to their distinctive circular structure and gene regulatory functions, establishing them as a significant class of functional non-coding in eukaryotes. Studies demonstrated that circRNAs can interact with RNA-binding proteins (RBPs), which play crucial roles tumorigenesis, metastasis, drug response cancer by influencing expression altering the processes tumor initiation progression. This review aims summarize recent advances research on circRNA-protein interactions (CPIs) discuss functions mode action CPIs at various stages expression, including transcription, splicing, translation, post-translational modifications context cancer. Additionally, we explore role resistance gain deeper understanding potential applications development new anti-cancer therapeutic approaches.

Language: Английский

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CASC8 activates the pentose phosphate pathway to inhibit disulfidptosis in pancreatic ductal adenocarcinoma though the c-Myc-GLUT1 axis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 27, 2025

Abstract Purpose Glucose starvation induces the accumulation of disulfides and F-actin collapse in cells with high expression SLC7A11, a phenomenon termed disulfidptosis. This study aimed to confirm existence disulfidptosis pancreatic ductal adenocarcinoma (PDAC) elucidate role Cancer Susceptibility 8 (CASC8) this process. Methods The PDAC was assessed using flow cytometry staining. CASC8 its clinical correlations were analyzed data from Genome Atlas (TCGA) further verified by chromogenic situ hybridization assay tissues. Cells knockdown overexpression subjected cell viability, EdU, transwell assays, used establish subcutaneous orthotopic tumor models. Disulfidptosis detected immunofluorescence assays. RNA sequencing metabolomics analysis performed determine metabolic pathways which significantly affected after knockdown. We glucose consumption NADP + /NADPH ratio investigate alterations profiles. immunoprecipitation combined fluorescence identify protein-RNA interactions. Protein stability, western blotting quantitative real-time PCR assays reveal potential molecular mechanism. Results observed could be rescued inhibitors. higher samples compared normal tissue. High correlated poor prognosis for patients contributed cancer progression vitro vivo. Furthermore, associated resistance under conditions PDAC. Mechanistically, interacted c-Myc enhance stability protein, leading activation pentose phosphate pathway, reduction ultimately inhibiting conditions. Conclusions provides evidence reveals upregulation malignancy. we demonstrate that acts as crucial regulator pathway disulfidptosis, thereby promoting progression.

Language: Английский

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Small extracellular vesicles (sEVs) in pancreatic cancer progression and diagnosis

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 269 - 282

Published: Feb. 6, 2025

Language: Английский

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The role of extracellular vesicles in circulating tumor cell-mediated distant metastasis

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

Published: Nov. 30, 2023

Current research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant metastasis. Primary tumors shed released into bloodstream to form CTCs referred as seeds colonize grow soil-like target organs, while EVs nontumor origin act fertilizers There is no previous text provides a comprehensive review role on during In this paper, we reviewed mechanisms metastasis, including ability enhance shedding CTCs, protect circulation determine direction CTC thus affecting metastasis tumors.

Language: Английский

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