Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер unknown, С. 106596 - 106596
Опубликована: Дек. 1, 2024
Язык: Английский
Exploration, Год журнала: 2024, Номер unknown
Опубликована: Июнь 26, 2024
Abstract The immunosuppressive microenvironment of glioblastoma multiforme (GBM) severely impacts the response to various treatments, including systemic chemotherapy. Targeted reprogramming GBM using RNA interference (RNAi) is largely restricted by poor brain delivery efficiency and targeting specificity. Herein, an acid‐cleavable transferrin (Tf) decorated engineering exosome‐based brain‐targeting system (ACTE) was proposed efficiently deliver small towards transform growth factor‐β (siTGF‐β) doxorubicin (DOX) site for combination chemo‐immunotherapy. siTGF‐β DOX co‐loaded ACTE, termed as DOX&siTGF‐β@ACTE (Ds@ACTE), designed specifically recognize Tf receptor (TfR) on blood‐brain barrier (BBB). Subsequently, Ds@ACTE undergoes acid‐responsive detachment within lysosome capillary endothelial cells, leading separation DOX&siTGF‐β@Exo (Ds@Exo) from Tf‐TfR complex enhanced BBB transcytosis. After crossing BBB, separated Ds@Exo can further target cells via homing effect. In vivo studies validated that significantly downregulated TGF‐β expression reprogram microenvironment, thereby reinforce chemotherapeutic effect DOX‐induced anti‐tumor immune response. effectiveness this strategy not only provide thinking designing a more intelligent based engineered exosomes but also explore effective treatment regimen GBM.
Язык: Английский
Процитировано
20
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7715 - 7715
Опубликована: Июль 14, 2024
Exosomes are small vesicles containing proteins, nucleic acids, and biological lipids, which responsible for intercellular communication. Studies have shown that exosomes can be utilized as effective drug delivery vehicles to accurately deliver therapeutic substances target tissues, enhancing effects reducing side effects. Mesenchymal stem cells (MSCs) a class of widely used tissue engineering, regenerative medicine, immunotherapy. derived from MSCs special immunomodulatory functions, low immunogenicity, the ability penetrate tumor high yield, expected engineered into efficient systems. Despite promising promise MSC-derived exosomes, exploring their optimal preparation methods, drug-loading modalities, potential remains challenging. Therefore, this article reviews related characteristics, application, risks systems in order find breakthroughs.
Язык: Английский
Процитировано
15
View, Год журнала: 2024, Номер 5(4)
Опубликована: Июль 18, 2024
Abstract With the aging and obesity era, increasing incidence of diabetes diabetic complications, especially non‐healing wounds, imposes a serious economic burden on both patients society. The complex microenvironments, including hyperglycemia, bacterial infection, ischemia, nerve damage, lead to prolonged inflammation proliferation phase wounds. Mesenchymal stem cell‐derived small extracellular vesicles (MSC‐sEVs), which contain rich variety therapeutic molecules, have been chased for decades because their potential roles in cellular communication, tissue regeneration, drug delivery. As powerful tools controlled‐sustained release sEVs, biocompatible hydrogels applied wide range biomedical applications. Herein, we first summarize pathological features such as angiopathy, neuropathy, immune cell dysfunction. Then, discuss biological properties, performance, stability pure MSC‐sEVs. After that, components, application patterns, responsiveness hydrogels. Next, loading avenues MSC‐sEVs into hydrogel, behaviors sEVs from hydrogels, influence crosslinking method hydrogel‐sEV composites. Finally, provide an overview current applications loaded with novel cell‐free engineering system managing wounds propose critical unsolved issues. This review is expected meaningful guidance developing wound management.
Язык: Английский
Процитировано
10
Life Sciences, Год журнала: 2024, Номер 354, С. 122985 - 122985
Опубликована: Авг. 14, 2024
Язык: Английский
Процитировано
7
Molecular Pharmaceutics, Год журнала: 2025, Номер unknown
Опубликована: Янв. 8, 2025
Traditional chemotherapy often encounters failure attributed to drug resistance mediated by tumor-repopulating cells (TRCs) and chemotherapy-triggered immune suppression. The effective inhibition of TRCs the mitigation drug-induced suppression are pivotal for successful chemotherapy. Here, TRC-derived microparticles (3D-MPs), characterized excellent tumor-targeting high TRC uptake properties, utilized deliver metformin chemotherapeutic doxorubicin ((DOX+Met)@3D-MPs). (DOX+Met)@3D-MPs efficiently enhance tumor accumulation highly internalized in TRCs. Additionally, significantly decrease upregulation P-glycoprotein expression intracellular retention, resulting increased sensitivity immunogenic cell death improved antitumor immunity. Importantly, also remarkably reduce chemotherapy-induced PD-L1 expression, alleviating facilitated PD-L1/PD-1 axis further immunological response against malignancy. These results underscore (DOX+Met)@3D-MPs' potential as a viable platform augmenting efficacy therapies.
Язык: Английский
Процитировано
0
Advanced Science, Год журнала: 2025, Номер unknown
Опубликована: Янв. 16, 2025
Abstract Targeted delivery of therapeutic agents is a persistent challenge in modern medicine. Recent efforts this area have highlighted the utility extracellular vesicles (EVs) as drug carriers, given that they naturally occur bloodstream and tissues, can be loaded with wide range molecules. However, biodistribution tissue tropism EVs remain difficult to study systematically. Here, multiplexed approach developed for simultaneous tracking from various cell lines within single vivo experiment. are used 16 different lines, through controlled fusion lipid nanoparticles (LNPs) carrying single‐stranded DNA barcodes, uniquely barcoded hybrid EV particle (hEV) library generated. These hEVs combined profiling mice, discovered HAP1‐derived demonstrated lung tropism, suggesting these may targeted into tissue. To examine possibility further, it shown HAP1 hEV Cre mRNA displayed functional lungs. Overall, technology enables rapid across sources, which poised improve throughput extent studies, while reducing number animals required research.
Язык: Английский
Процитировано
0
Journal of Controlled Release, Год журнала: 2025, Номер 380, С. 664 - 685
Опубликована: Фев. 17, 2025
Язык: Английский
Процитировано
0
Obesity Medicine, Год журнала: 2025, Номер unknown, С. 100597 - 100597
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
International Journal of Biological Macromolecules, Год журнала: 2025, Номер 307, С. 141957 - 141957
Опубликована: Март 10, 2025
Язык: Английский
Процитировано
0
Exploration, Год журнала: 2025, Номер unknown
Опубликована: Март 6, 2025
ABSTRACT Stroke remains the leading cause of neurological mortality and disability worldwide, with post‐stroke inflammation significantly hindering neural repair. Despite its critical impact, mechanism‐based therapeutic strategies are scarce. In this study, we uncovered a critically important yet previously unexamined cell population, p21 + CD86 microglia, which accumulated in ischemic region. Unexpectedly, discovered that interacted C/EBPβ, driving C/EBPβ‐dependent transcription upregulating key pro‐inflammatory factors such as Il6 , Il1β Cxcl2 Cxcl10 . To specifically target eliminate these pathogenic engineered exosomes peptide selectively binds microglia loaded them senolytic Quercetin. Furthermore, developed an optimized, stable Que@micro‐Exo formulation. Systemic administration robustly reduced suppressed their phenotype. Notably, functional analyses revealed treatment mitigated blood‐brain barrier disruption, promoted beneficial microglial polarization, decreased neutrophil infiltration, enhanced recovery following cerebral ischemia, all favorable safety profile. Our preclinical findings lay foundation for targeting novel strategy, highlighting potential exosome‐based anti‐inflammatory therapy stroke other central nervous system disorders.
Язык: Английский
Процитировано
0