Effects of 5-fluorouracil, thymoquinone, and mammary stem cells' exosomes on in vitro cultured breast cancer cells.

Background: 5-fluorouracil (5-FU) is an antimetabolic agent used for treating slowly growing solid tumors like breast and ovarian carcinoma. Thymoquinone (TQ) is the main biologically active constituent of Nigella sativa, it has been found to demonstrate anticancerous effects in several preclinical studies, and this is because TQ possesses multitarget nature. Stem cells-derived exosomes are in the spotlight of research and are promising tissue regenerative and anticancer cell-derived nanovesicles. Aim: Herein, we studied the antineoplastic effects of Exosomes derived from mammary stem cells (MaSCs-Exo) on breast cancer cells, alone or combined with TQ when compared to a breast cancer chemotherapeutic agent; 5-FU. Methods: Our approach included performing viability test and measuring the expression of pro-apoptotic gene (Bax), anti-apoptotic gene (BCL-2) and angiogenic gene (VEGF) on Human MCF-7 cells (breast adenocarcinoma cells), the MCF-7 cells were cultured and incubated with medium containing 5-FU (25 µg/ml), TQ (200 µg/ml), MaSCs-Exo (100 µg protein equivalent), a combination of TQ (200 µg/ml) and MaSCs-Exo (100 µg). Results: Our obtained results show that TQ and MaSCs-Exo each can effectively inhibit breast cancer cell line (MCF-7) proliferation and growth. Also, the results show that the combination of TQ and MaSCs-Exo had higher cytotoxic effects on MCF-7 breast cancer cells than TQ or 5-FU, alone. Conclusion: The present study shows a promising anticancer potential of exosomes isolated from mammary stem cells; this effect was potentiated by adding TQ with MaSCs-derived exosomes.

Emerging role of exosomes as a liquid biopsy tool for diagnosis, prognosis & monitoring treatment response of communicable & non-communicable diseases.

ABSTRACT: From an initial thought of being used as a cellular garbage bin to a promising target for liquid biopsies, the role of exosomes has drastically evolved in just a few years of their discovery in 1983. Exosomes are naturally secreted nano-sized vesicles, abundant in all types of body fluids and can be isolated intact even from the stored biological samples. Being stable carriers of genetic material (cellular DNA, mRNA and miRNA) and having specific cargo (signature content of originating cells), exosomes play a crucial role in pathogenesis and have been identified as a novel source of biomarkers in a variety of disease conditions. Recently exosomes have emerged as a promising 'liquid biopsy tool'and have shown great potential in the field of non-invasive disease diagnostics, prognostics and treatment response monitoring in both communicable as well as non-communicable diseases. However, there are certain limitations to overcome which restrict the use of exosome-based liquid biopsy as a gold standard testing procedure in routine clinical practices. The present review summarizes the current knowledge on the role of exosomes as the liquid biopsy tool in diagnosis, prognosis and treatment response monitoring in communicable and non-communicable diseases and highlights the major limitations, technical advancements and future prospects of the utilization of exosome-based liquid biopsy in clinical interventions.

Cancer-derived exosomes as novel biomarkers in metastatic gastrointestinal cancer.

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

Exosomal microRNAs as potential biomarkers and therapeutic targets in corneal diseases.

Exosomes are a subtype of extracellular vesicle (EV) that are released and found in almost all body fluids. Exosomes consist of and carry a variety of bioactive molecules, including genetic information in the form of microRNAs (miRNAs). miRNA, a type of small non-coding RNA, plays a key role in regulating genes by suppressing their translation. miRNAs are often disrupted in the pathophysiology of different conditions, including eye disease. The stability and easy detectability of exosomal miRNAs in body fluids make them promising biomarkers for the diagnosis of different diseases. Additionally, due to the natural delivery capabilities of exosomes, they can be modified to transport therapeutic miRNAs to specific recipient cells. Most exosome research has primarily focused on cancer, so there is limited research highlighting the importance of exosomes in ocular biology, particularly in cornea-associated pathologies. This review provides an overview of the existing evidence regarding the primary functions of exosomal miRNAs and their potential role in diagnostic and therapeutic applications in the human cornea.

Myofibroblast-derived exosomes enhance macrophages to myofibroblasts transition and kidney fibrosis.

A critical event in the pathogenesis of kidney fibrosis is the transition of macrophages into myofibroblasts (MMT). Exosomes play an important role in crosstalk among cells in the kidney and the development of renal fibrosis. However, the role of myofibroblast-derived exosomes in the process of MMT and renal fibrosis progression remains unknown. Here, we examined the role of myofibroblast-derived exosomes in MMT and kidney fibrogenesis. In vitro, transforming growth factor-ß1 stimulated the differentiation of kidney fibroblasts into myofibroblasts and promoted exosome release from myofibroblasts. RAW264.7 cells were treated with exosomes derived from myofibroblasts. We found purified exosomes from myofibroblasts trigger the MMT. By contrast, inhibition of exosome production with GW4869 or exosome depletion from the conditioned media abolished the ability of myofibroblasts to induce MMT. Mice treatment with myofibroblast-derived exosomes (Myo-Exo) exhibited severe fibrotic lesion and more abundant MMT cells in kidneys with folic acid (FA) injury, which was negated by TANK-banding kinase-1 inhibitor. Furthermore, suppression of exosome production reduced collagen deposition, extracellular matrix protein accumulation, and MMT in FA nephropathy. Collectively, Myo-Exo enhances the MMT and kidney fibrosis. Blockade of exosomes mediated myofibroblasts-macrophages communication may provide a novel therapeutic target for kidney fibrosis.

Exosomal ncRNAs: Multifunctional contributors to the immunosuppressive tumor microenvironment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant liver cancer characterized by aggressive progression, unfavorable prognosis, and an increasing global health burden. Therapies that precisely target immunological checkpoints and immune cells have gained significant attention as possible therapeutics in recent years. In truth, the efficacy of immunotherapy is heavily contingent upon the tumor microenvironment (TME). Recent studies have indicated that exosomes serve as a sophisticated means of communication among biomolecules, executing an essential part in the TME of immune suppression. Exosomal non-coding RNAs (ncRNAs) can induce the activation of tumor cells and immunosuppressive immune cells that suppress the immune system, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), CD+8 T cells, regulatory T cells (Tregs), and regulatory B cells (Bregs). This cell-cell crosstalk triggered by exosomal ncRNAs promotes tumor proliferation and metastasis, angiogenesis, malignant phenotype transformation, and drug resistance. Hence, it is imperative to comprehend how exosomal ncRNAs regulate tumor cells or immune cells within the TME to devise more comprehensive and productive immunotherapy programs. This study discusses the features of exosomal ncRNAs in HCC and how the activation of the exosomes redefines the tumor's immunosuppressive microenvironment, hence facilitating the advancement of HCC. Furthermore, we also explored the potential of exosomal ncRNAs as a viable biological target or natural vehicle for HCC therapy.

Exploring the dynamic interplay between exosomes and the immune tumor microenvironment: implications for breast cancer progression and therapeutic strategies.

Breast cancer continues to pose a substantial worldwide health concern, demanding a thorough comprehension of the complex interaction between cancerous cells and the immune system. Recent studies have shown the significant function of exosomes in facilitating intercellular communication and their participation in the advancement of cancer. Tumor-derived exosomes have been identified as significant regulators in the context of breast cancer, playing a crucial role in modulating immune cell activity and contributing to the advancement of the illness. This study aims to investigate the many effects of tumor-derived exosomes on immune cells in the setting of breast cancer. Specifically, we will examine their role in influencing immune cell polarization, facilitating immunological evasion, and modifying the tumor microenvironment. Furthermore, we explore the nascent domain of exosomes produced from immune cells and their prospective involvement in the prevention of breast cancer. This paper focuses on new research that emphasizes the immunomodulatory characteristics of exosomes produced from immune cells. It also explores the possibility of these exosomes as therapeutic agents or biomarkers for the early identification and prevention of breast cancer. The exploration of the reciprocal connections between exosomes formed from tumors and immune cells, together with the rising significance of exosomes derived from immune cells, presents a potential avenue for the advancement of novel approaches in the field of breast cancer therapy and prevention.

Breast cancer derived exosomes: Theragnostic perspectives and implications.

Breast cancer (BC) is the most prevalent malignancy affecting women worldwide. Although conventional treatments such as chemotherapy, surgery, hormone therapy, radiation therapy, and biological therapy are commonly used, they often entail significant side effects. Therefore, there is a critical need to investigate more cost-effective and efficient treatment modalities in BC. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, play a crucial role in modulating recipient cell behaviour and driving cancer progression. Among the EVs, exosomes provide valuable insights into cellular dynamics under both healthy and diseased conditions. In cancer, exosomes play a critical role in driving tumor progression and facilitating the development of drug resistance. BC-derived exosomes (BCex) dynamically influence BC progression by regulating cell proliferation, immunosuppression, angiogenesis, metastasis, and the development of treatment resistance. Additionally, BCex serve as promising diagnostic markers in BC which are detectable in bodily fluids such as urine and saliva. Targeted manipulation of BCex holds significant therapeutic potential. This review explores the therapeutic and diagnostic implications of exosomes in BC, underscoring their relevance to the disease. Furthermore, it discusses future directions for exosome-based research in BC, emphasizing the necessity for further exploration in this area.

Shaping the immune-suppressive microenvironment on tumor-associated myeloid cells through tumor-derived exosomes.

Tumor-associated myeloid cells (TAMCs) play a crucial role in orchestrating the dynamics of the tumor immune microenvironment. This heterogeneous population encompasses myeloid-derived suppressor cells, tumor-associated macrophages and dendritic cells, all of which contribute to the establishment of an immunosuppressive milieu that fosters tumor progression. Tumor-derived exosomes (TEXs), small extracellular vesicles secreted by tumor cells, have emerged as central mediators in intercellular communication within the tumor microenvironment. In this comprehensive review, we explore the intricate mechanisms through which TEXs modulate immune-suppressive effects on TAMCs and their profound implications in cancer progression. We delve into the multifaceted ways in which TEXs influence TAMC functions, subsequently affecting tumor immune evasion. Furthermore, we elucidate various therapeutic strategies aimed at targeting TEX-mediated immune suppression, with the ultimate goal of bolstering antitumor immunity.

Diagnostic value of plasma-derived exosomal miR-223 for epithelial ovarian cancer.

OBJECTIVES: To evaluate the diagnostic value of plasma exosomal miR-223 and its combination with CA125 for the diagnosis of early-stage epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Exosomes derived from the plasma of 78 EOC patients, 40 patients with epithelial benign ovarian tumors, and 52 healthy participants were isolated using the ultracentrifugation method and identified by transmission electron microscopy (TEM) and western blot. RESULTS: The expression of exosomal miR-223 was significantly upregulated in the plasma of EOC patients compared to that in healthy subjects and patients with benign diseases. The combination of exosomal miR-223 and CA125 from plasma had an equivalent area under the ROC curve (AUC) to CA125 alone for discriminating between EOC and non-EOC cases, including healthy subjects and benign ovarian tumors. However, the AUC value of the combination was 0.944 (95% CI: 0.899-0.990) for differentially diagnosing early-stage EOC from healthy subjects, slightly higher than that of CA125 alone (0.928, 95% CI: 0.875-0.981), with a sensitivity and specificity of 0.9784 and 0.885, respectively. CONCLUSION: Our data suggest that plasma exosomal miR-223 can be used as a complement to CA125 to increase the diagnostic power for differentiating early-stage EOC from healthy subjects.

[Exosome and prevention of Alzheimer's disease: based on theory of kidney storing essence].

The theory of kidney storing essence storage, an important part of the basic theory of traditional Chinese medicine(TCM), comes from the Chapter 9 Discussion on Six-Plus-Six System and the Manifestations of the Viscera in the Plain Questions, which says that "the kidney manages closure and is the root of storage and the house of Jing(Essence)". According to this theory, essence is the fundamental substance of human life activities and it is closely related to the growth and development of the human body. Alzheimer's disease(AD) is one of the common neurodegenerative diseases, with the main pathological features of Aß deposition and Tau phosphorylation, which activate neurotoxic reactions and eventually lead to neuronal dysfunction and cell death, severely impairing the patient's cognitive and memory functions. Although research results have been achieved in the TCM treatment of AD, the complex pathogenesis of AD makes it difficult to develop the drugs capable of curing AD. The stem cell therapy is an important method to promote self-repair and regeneration, and bone marrow mesenchymal stem cells(BMSCs) as adult stem cells have the ability of multi-directional differentiation. By reviewing the relevant literature, this paper discusses the association between BMSCs and the TCM theory of kidney storing essence, and expounds the material basis of this theory from the perspective of molecular biology. Studies have shown that TCM with the effect of tonifying the kidney in the treatment of AD are associated with BMSCs. Exosomes produced by such cells are one of the main substances affecting AD. Exosomes containing nucleic acids, proteins, and lipids can participate in intercellular communication, regulate cell function, and affect AD by reducing Aß deposition, inhibiting Tau protein phosphorylation and neuroinflammation, and promoting neuronal regeneration. Therefore, discussing the prevention and treatment of exosomes and AD based on the theory of kidney storing essence will provide a new research idea for the TCM treatment of AD.

Urinary Exosomal miR-17-5p Accelerates Bladder Cancer Invasion by Repressing its Target Gene ARID4B and Regulating the Immune Microenvironment.

BACKGROUND: Urothelial bladder cancer (BCa) is a common malignant tumor of the urinary system. It has been identified that exosomal miRNAs contribute to the development of BCa. However, its significance and mechanism in the malignant biological behavior of BCa remain unclear. In this study, the influence of exosomal miRNAs on BCa progression was investigated. METHODS: High-throughput sequencing was conducted to analyze the microRNA-expression profile in urinary exosomes to screen out the key miRNA of muscle-invasive bladder cancer (MIBC). Then, candidate miRNA expression was verified and validated in urinary exosomes and tissue samples. To address the potential role of the candidate miRNA, we overexpressed and knocked down the candidate miRNA and explored its activity in BCa cell lines. Furthermore, the target gene of the selected miRNA was predicted and validated. RESULTS: The expression profile of miRNAs revealed increased expression of miR-17-5p in MIBC urinary exosomes, and this was later confirmed in urinary exosomes and tissue samples. Cell function studies revealed that exosomal miR-17-5p significantly promoted the growth and invasion of BCa cells. Bioinformatics and luciferase experiments demonstrated that the ARID4B mRNA 3' UTR might be the binding site for miR-17-5p. Low ARID4B levels were linked to high-grade BCa patients and were associated with a better prognosis. CONCLUSION: Elevated miR-17-5p contributes to BCa progression by targeting ARID4B and influencing the immune system. Based on these findings, miR-17-5p has the potential to be a new therapeutic target for the treatment of BCa.

Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC), a lethal disease, requires a grasp of its biology for effective therapies. Exosomes, implicated in cancer, are poorly understood in living systems. Here we use the genetically engineered mouse model (ExoBow) to map the spatiotemporal distribution of exosomes from healthy and PDAC pancreas in vivo to determine their biological significance. We show that, within the PDAC microenvironment, cancer cells establish preferential communication routes through exosomes with cancer associated fibroblasts and endothelial cells. The latter being a conserved event in the healthy pancreas. Inhibiting exosomes secretion in both scenarios enhances angiogenesis, underscoring their contribution to vascularization and to cancer. Inter-organ communication is significantly increased in PDAC with specific organs as most frequent targets of exosomes communication occurring in health with the thymus, bone-marrow, brain, and intestines, and in PDAC with the kidneys, lungs and thymus. In sum, we find that exosomes mediate an organized intra- and inter- pancreas communication network with modulatory effects in vivo.

Prediction of Response to Chemoradiotherapy by Dynamic Changes of Circulating Exosome Levels in Patients with Esophageal Squamous Cell Carcinoma.

Background: The exosomes-based liquid biopsy represents a prospective biomarker for tumor screening, prognosis prediction, and tumor regression. This study aimed to isolate circulating exosomes (CEs) from plasma of the esophageal squamous cell carcinoma (ESCC) patients who received chemoradiotherapy through exosome detection method via the ultrafast-isolation system (EXODUS) and investigated the association between the dynamic changes of CE levels and therapeutic effect. Methods: We isolated and quantitatively analyzed CEs from plasma of locally advanced ESCC patients received chemoradiotherapy at 2 time points: baseline (pre-chemoradiotherapy) and 2 months after the chemoradiotherapy (post-chemoradiotherapy). We isolated exosomes from plasma by EXODUS platform and confirmed them through nanoparticle tracking analysis (NTA), transmission electron microscope (TEM), and Western blot. The associations of CE level with clinicopathological characteristics, tumor regression, and progression-free survival (PFS) were analyzed. Results: The average diameter of CEs was 107.4±14.3 nm at baseline and 101.7±17.1 nm at post-chemoradiotherapy. The mean exosome concentration significantly decreased after chemoradiotherapy (7.3×1011 particles/mL vs 5.4×1011 particles/mL, P < 0.001). The patients with stage III-IVA and tumor length ≥5cm had obviously higher baseline CE levels. Dynamic changes in CE levels were successfully applied for evaluation of chemoradiotherapy response and PFS. Furthermore, through multivariate Cox regression analysis, it was revealed that dynamic changes of CE levels were an independent predictor of PFS in locally advanced ESCC patients who received chemoradiotherapy. Conclusion: Here, we demonstrated EXODUS platform isolated and enriched CEs from plasma of ESCC patients with high-purity and high-yield. The EXODUS platform can facilitate liquid biopsy based on exosomes translation to the clinic. Baseline CE levels can reflect ESCC tumor burden. The dynamic changes of CE levels during chemoradiotherapy allow the prediction of treatment effect and PFS of ESCC patients, requiring further investigations in larger patient cohorts.

Cellular and Exosomal MicroRNAs: Emerging Clinical Relevance as Targets for Breast Cancer Diagnosis and Prognosis.

Breast cancer accounts for the highest cancer cases globally, with 12% of occurrences progressing to metastatic breast cancer with a low survival rate and limited effective early intervention strategies augmented by late diagnosis. Moreover, a low concentration of prognostic and predictive markers hinders disease monitoring. Circulating and exosomal microRNAs (miRNAs) have recently shown a considerable interplay in breast cancer, standing out as effective diagnostic and prognostic markers. The primary functions are as gene regulatory agents at the genetic and epigenetic levels. An array of dysregulated miRNAs stimulates cancer-promoting mechanisms, activating oncogenes and controlling tumor-suppressing genes and mechanisms. Exosomes are vastly studied extracellular vesicles, carrying, and transporting cargo, including noncoding RNAs with premier roles in oncogenesis. Translocation of miRNAs from the circulation to exosomes, with RNA-binding proteins in stress-induced conditions, has shown significant cooperation in function to promote breast cancer. This review examines cellular and exosomal miRNA biogenesis and loading, the clinical implications of their dysregulation, their function in diagnosis, prognosis, and prediction of breast cancer, and in regulating cancer signaling pathways. The influence of cellular and exosomal miRNAs presents clinical significance on breast cancer diagnosis, subtyping, staging, prediction, and disease monitoring during treatment, hence a potent marker for breast cancer.

Exosomes From IgE-Stimulated Mast Cells Aggravate Asthma-Mediated Atherosclerosis Through circRNA CDR1as-Mediated Endothelial Cell Dysfunction in Mice.

BACKGROUND: IgE has been known for mediating endothelial cell dysfunction and mast cell (MC) activation to fuel asthma-aggravated high-fat diet-induced atherosclerosis. However, it remains unclear for the mechanism of asthma-mediated atherosclerosis, especially the potential involvement of IgE in the exacerbation of asthma-mediated atherosclerosis with a standard laboratory diet, and the cross talk between endothelial cells and MCs. METHODS: Asthma-mediated atherosclerosis mice models under a standard laboratory diet and FcεR1 knock-out mice were used to determine the role of IgE-FcεR1 signaling in asthma-mediated atherosclerosis, which was assessed by Oil Red O staining and immunohistochemistry. Various in vitro assays including nanoparticle tracking analysis and transmission electron microscopy were used to evaluate exosome characteristics. Immunofluorescence and fluorescent in situ hybridization approaches were used to evaluate the effect and mechanism of MC-secreted exosomes encapsulated circular RNA CDR1as (cerebellar degeneration-related 1 antisense) on endothelial cells in vivo and in vitro. Finally, cohort studies examined the plasma CDR1as levels in patients with atherosclerosis with or without allergies. RESULTS: Asthma mice with a standard laboratory diet showed increased atherosclerotic lesions and inflammatory infiltration depending on IgE-FcεR1 signal. FcεR1 knockout mice and blockage of IgE-FcεR1 signaling with IgE monoclonal antibody, omalizumab, all significantly alleviated asthma-mediated atherosclerosis and vascular inflammatory remodeling. Anti-inflammation with dexamethasone and stabilization of MC with cromolyn partially alleviated atherosclerotic lesions and mitigated the inflammatory infiltration in arteries. Mechanistically, IgE stimulation upregulates MC CDR1as expression in exosomes and upregulates the endothelial cell adhesive factors VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) via the CDR1as-FUS (fused in sarcoma)-phos-p65 axis. Knockdown of CDR1as in vivo significantly decreased the endothelial adhesion function and mitigated asthma-mediated atherosclerosis. Furthermore, a cohort study indicated higher plasma CDR1as levels in patients with atherosclerosis with allergies than in patients with atherosclerosis and healthy controls. CONCLUSIONS: Exosomes from IgE-stimulated MCs aggravated atherosclerosis through circular RNA CDR1as-mediated endothelial dysfunction, providing a novel insight into asthma-mediated atherosclerosis and potential diagnostic and therapeutic targets.

Communication between nonalcoholic fatty liver disease and atherosclerosis: Focusing on exosomes.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disorder on a global scale. Atherosclerosis (AS), a leading cause of cardiovascular diseases, stands as the primary contributor to mortality among patients diagnosed with NAFLD. However, the precise etiology by which NAFLD causes AS remains unclear. Exosomes are nanoscale extracellular vesicles secreted by cells, and are considered to participate in complex biological processes by promoting cell-to-cell and organ-to-organ communications. As vesicles containing protein, mRNA, non-coding RNA and other bioactive molecules, exosomes can participate in the development of NAFLD and AS respectively. Recently, studies have shown that NAFLD can also promote the development of AS via secreting exosomes. Herein, we summarized the recent advantages of exosomes in the pathogenesis of NAFLD and AS, and highlighted the role of exosomes in mediating the information exchange between NAFLD and AS. Further, we discussed how exosomes play a prominent role in enabling information exchange among diverse organs, delving into a novel avenue for investigating the link between diseases and their associated complications. The future directions and emerging challenges are also listed regarding the exosome-based therapeutic strategies for AS under NAFLD conditions.

Modification of immune cell-derived exosomes for enhanced cancer immunotherapy: current advances and therapeutic applications.

Cancer immunotherapy has revolutionized the approach to cancer treatment of malignant tumors by harnessing the body's immune system to selectively target cancer cells. Despite remarkable advances, there are still challenges in achieving successful clinical responses. Recent evidence suggests that immune cell-derived exosomes modulate the immune system to generate effective antitumor immune responses, making them a cutting-edge therapeutic strategy. However, natural exosomes are limited in clinical application due to their low drug delivery efficiency and insufficient antitumor capacity. Technological advancements have allowed exosome modifications to magnify their intrinsic functions, load different therapeutic cargoes, and preferentially target tumor sites. These engineered exosomes exert potent antitumor effects and have great potential for cancer immunotherapy. In this review, we describe ingenious modification strategies to attain the desired performance. Moreover, we systematically summarize the tumor-controlling properties of engineered immune cell-derived exosomes in innate and adaptive immunity. Collectively, this review provides a comprehensive and intuitive guide for harnessing the potential of modified immune cell-derived exosome-based approaches, offering valuable strategies to enhance and optimize cancer immunotherapy.

Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy.

Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin with a diameter of 30-150 nm, play a critical role in intercellular communication and have become an ideal vehicle for drug delivery. A growing body of evidence suggests that exosomes have great potential for repairing SCI. In this review, we introduce exosome preparation, functions, and administration routes. In addition, we summarize the effect and mechanism by which various exosomes repair SCI and review the efficacy of exosomes in combination with other strategies to repair SCI. Finally, the challenges and prospects of the use of exosomes to repair SCI are described.