Mesenchymal stem cell (MSC) therapy, with its unique properties, has garnered interest in cancer treatment. Exosomes (EXOs)-derived from MSC retain the paracrine components of MSCs and demonstrate increased stability, minimal immunogenicity, and low risk of unintended tumorigenesis. Enhanced endocytosis methods make them versatile delivery vehicles for therapeutic cargo. MSC-EXOs can either promote or inhibit carcinogenesis, mediated by paracrine factors and various RNA molecules, particularly microRNAs (miRNAs). The prospect of using MSC-EXOs as a delivery tool for antitumor miRNAs in solid tumor therapy is promising. Exosomes' intrinsic tumor-targeting abilities and low immunogenicity make them ideal for delivering miRNAs, which have shown potential as cancer therapeutics. miRNAs within MSC-EXOs molecules can stimulate tumor growth or induce non-apoptotic cell death pathways, such as ferroptosis, depending on context. Ferroptosis is a kind of controlled cell death that is associated with the pathophysiology of several illnesses and includes iron metabolism. There is growing evidence that miRNAs carried by exosomes derived from MSCs may control ferroptosis in tumor cells by altering key genes related to antioxidant defense, lipid peroxidation, and iron metabolism. Understanding their complex mechanisms in the tumor microenvironment and optimizing their cargo are critical steps toward harnessing their full therapeutic potential. This review provides a comprehensive overview of MSC-EXOs and their role in cancer treatment. We also discuss the potential of MSC-EXOs as delivery vehicles for miRNAs to enhance therapeutic efficacy, as well as the role of exosomal miRNAs in the induction of ferroptosis.

Most eukaryotic cells secrete extracellular vesicles called exosomes, which are involved in intercellular communication. Exosomes play a role in tumor development and metastasis by transporting bioactive chemicals from cancerous cells to other cells in local and distant microenvironments. However, the potential of exosomes can be used by engineering them and considering different therapeutic approaches to overcome tumors. Exosomes are a promising drug delivery approach that can help decrease side effects from traditional treatments like radiation and chemotherapy by acting as targeted agents at the tumor site. The present review provides an overview of exosomes and various aspects of the role of exosomes in cancer development, which include these items: exosomes in cancer diagnosis, exosomes and drug delivery, exosomes and drug resistance, exosomal microRNAs and exosomes in tumor microenvironment, etc. Cancer stem cells release exosomes that nurture tumors, promoting unwanted growth and regeneration, and these types of exosomes should be inhibited. Ironically, exosomes from other cells, such as hepatocytes or mesenchymal stem cells (MSCs), are vital for healing organs like the liver and repairing gastric ulcers. Without proper treatment, this healing process can backfire, potentially leading to disease progression or even cancer. What can be found from various studies about the role of exosomes in the field of cancer is that exosomes act like a double-edged sword; on the other hand, natural exosomes in the body may play an important role in the process and progression of cancer, but by engineering exosomes, they can be directed towards target therapy and targeted delivery of drugs to tumor cells. By examining the role and application of exosomes in various mechanisms of cancer, it is possible to help treat this disease more efficiently and quickly in preclinical and clinical research.

Hepatocellular carcinoma (HCC) represents a multifaceted and aggressive cancer frequently associated with chronic inflammation and immune cell activation. The pathogenesis of HCC is influenced by a variety of factors such as long non-coding RNAs (lncRNAs). LncRNAs, a significant class of non-coding RNAs, contribute to the intricate nature of the transcriptome and are extensively distributed across various tissues and cell types in mammals. In HCC, these transcripts are crucial not only for deepening our molecular understanding but also for advancing clinical outcomes, as they serve as both oncogenes and tumor suppressors by dysregulating essential genes and signaling pathways. Additionally, macrophage polarization is crucial in HCC tumor progression. The study explores the role of lncRNAs in hepatocellular carcinoma (HCC) and elucidates the specific molecular mechanisms by which key lncRNAs such as HULC and MALAT1 regulate macrophage polarization in the tumor microenvironment. These lncRNAs modulate cytokine profiles and influence immune regulators including IL-10 and TGF-β, steering macrophages toward an M2-like, pro-tumor phenotype that fosters aggressive tumor characteristics and progression. Mechanistically, these transcripts interact with epigenetic modifiers like EZH2 to alter histone modifications and chromatin accessibility, while also stabilizing mRNAs that encode inflammatory mediators, thereby reinforcing an immunosuppressive response. The clinical implications of these findings are substantial. The detection of such lncRNAs in patient samples offers a minimally invasive diagnostic avenue, while their pivotal role in complex immune cell behavior positions them as promising prognostic biomarkers. Moreover, targeting these lncRNAs may lead to innovative therapeutic strategies aimed at disrupting tumor-supportive inflammatory cascades and restoring an effective antitumor immune response. Understanding the intricate interplay between lncRNA-mediated epigenetic regulation and macrophage polarization not only refines our grasp of HCC progression but also opens new pathways for interventions designed to improve patient outcomes.

Hepatocellular carcinoma (HCC) is a significant global health concern and ranks as the third leading cause of cancer-associated mortality. Systemic therapy faces the emergence of resistance, which hinders the clinical benefits. Recent evidence suggests that exosomes, measuring between 30 and 150 nm in size, which impact the antitumor immune responses, making them a promising candidate for cancer immunotherapy. Owing to their unique physical and chemical characteristics, exosomes can be tailored and engineered for a range of therapeutic objectives. In the present review, we outline the immunomodulatory functions of exosomes in the tumor microenvironment (TME) of HCC, aiming to decipher the underlying mechanisms of exosomes in remodeling suppressive TME. Moreover, we provide detailed and intuitive resource for leveraging the potential of exosomes in immunotherapy, presenting valuable strategies to improve and optimize HCC treatment. Despite the huge therapeutic potential of exosomes, significant challenges persist, including the need for standardization in exosome production, optimization of cargo loading techniques, and the assurance of safety and effectiveness in clinical applications. Addressing these challenges may pave the way for exosome-based immunotherapy for HCC patients.

Exosomes are vesicles secreted by cells, typically ranging from 30 to 150 nm in diameter, and serve as crucial mediators of intercellular communication. Exosomes are capable of loading various therapeutic substances, such as small molecule compounds, proteins, and oligonucleotides, thereby making them an ideal vehicle for drug delivery. The distinctive biocompatibility, high stability, and targeting properties of exosomes render them highly valuable for future treatments of diseases like cancer and cardiovascular diseases. Despite the potential advantage of exosomes in delivering biologically active molecules, the techniques for the preparation, purification, preservation, and other aspects of stem cell exosomes are not yet mature enough. In this paper, we briefly introduce the composition, biogenesis, and benefits of exosomes, and primarily focus on summarizing the isolation and purification methods of exosomes, the preparation of engineered exosomes, and their clinical applications, to better provide new ideas for the development of exosome drug delivery systems.

Breast cancer (BC) remains a complex and widespread problem, affecting millions of women worldwide, Among the various subtypes of BC, triple-negative breast cancer (TNBC) is particularly challenging, representing approximately 20% of all BC cases, and the survival rate of TNBC patients is generally worse than other subtypes of BC. TNBC is a heterogeneous disease characterized by lack of expression of three receptors: estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2), resulting conventional hormonal therapies are ineffective for its management. Despite various therapeutic approaches have been explored, but no definitive solution has been found yet for TNBC. Current treatments options are chemotherapy, immunotherapy, radiotherapy and surgery, although, these therapies have some limitations, such as the development of resistance to anti-cancer drugs, and off-target toxicity, which remain primary obstacles and significant challenges for TNBC. Several findings have shown that EVs exhibit significant therapeutic promise in many diseases, and a similar important role has been observed in various types of tumor. Studies suggest that EVs may offer a potential solution for the management of TNBC. This review highlights the multifaceted roles of EVs in TNBC, emphasizing their involvement in disease progression, diagnosis and therapeutic approach, as well as their potential as biomarkers and drug delivery.

Acute lung injury (ALI) which is caused by Staphylococcus aureus (SA), is a serious lung disease that threatens human health. Although some current treatments are effective in alleviating ALI, they still have a significant mortality rate. At present, adipose-derived mesenchymal stem cells (ADSCs)-derived extracellular vesicles (EVs) have been investigated for the treatment of various diseases. Here, we examined the role of ADSCs-derived EVs in regulating apoptosis and inflammation during ALI.

We showed that ADSCs and ADSCs-derived EVs supplementation could improve lung injury, restore mitochondrial function, and inhibit inflammation and apoptosis in ALI mice. Furthermore, miR-320a was present in EVs derived from ADSCs, and it can be transferred into lung tissue. In vitro, Casitas B-lineage lymphoma (CBL) expression was inhibited by miR-320a mimics. Finally, we found that miR-320a alleviated mitochondrial damage, inflammation, and apoptosis via the CBL/AMPK/JNK pathway.

In conclusion, EVs from ADSCs could alleviate ALI via the CBL/AMPK signaling pathway. Therefore, the purpose of our study was to investigate the application of ADSC-derived EVs in mitigating ALI by modulating metabolic processes.

Liver cancer, particularly hepatocellular carcinoma (HCC), remains a significant global health challenge due to its high mortality rate and late-stage diagnosis. The discovery of reliable biomarkers is crucial for improving early detection and patient outcomes. This review provides a comprehensive overview of current and emerging biomarkers for HCC, including alpha-fetoprotein, des-gamma-carboxy prothrombin, glypican-3, Golgi protein 73, osteopontin, and microRNAs. Despite advancements, the diagnostic limitations of existing biomarkers underscore the urgent need for novel markers that can detect HCC in its early stages. The review emphasizes the importance of integrating multi-omics approaches, combining genomics, proteomics, and metabolomics, to develop more robust biomarker panels. Such integrative methods have the potential to capture the complex molecular landscape of HCC, offering insights into disease mechanisms and identifying targets for personalized therapies. The significance of large-scale validation studies, collaboration between research institutions and clinical settings, and consideration of regulatory pathways for clinical implementation is also discussed. In conclusion, while substantial progress has been made in biomarker discovery, continued research and innovation are essential to address the remaining challenges. The successful translation of these discoveries into clinical practice will require rigorous validation, standardization of protocols, and cross-disciplinary collaboration. By advancing the development and application of novel biomarkers, we can improve the early detection and management of HCC, ultimately enhancing patient survival and quality of life.

Malignant tumors pose a significant threat to human health, and conventional cancer therapies are limited by inadequate targeting, leading to severe side effects. Exosomes, as extracellular vesicles mediating intercellular communication, exhibit advantages such as low immunogenicity, high biocompatibility, and low toxicity. After modification, engineered exosomes can be employed as targeted delivery vehicles in tumor therapy. This review summarizes the cellular origin, production methods, engineering strategies, and drug-loading routes of engineered exosomes, discusses their applications in cancer treatment, and delves into the challenges and issues in translating engineered exosomes to clinical practice, aiming to provide insights for exosome engineering research.

Exosome-based cancer immunotherapy is advancing quickly on the concept of artificially activating the immune system to combat cancer. They can mechanistically change the tumor microenvironment, increase immune responses, and function as efficient drug delivery vehicles because of their inherent bioactivity, low toxicity, and immunogenicity. Accurate identification of the mechanisms of action of exosomes in tumor environments, along with optimization of their isolation, purification, and characterization methods, is necessary to increase clinical applications. Exosomes can be modified through cargo loading and surface modification to enhance their therapeutic applications, either before or after the donor cells' isolation. These engineered exosomes can directly target tumor cells at the tumor site or indirectly activate innate and adaptive immune responses in the tumor microenvironment. This approach is particularly effective when combined with traditional cancer immunotherapy techniques such as vaccines, immune checkpoints, and CAR-T cells. It can improve anti-tumor responses, induce long-term immunity, and address the limitations of traditional therapies, such as poor penetration in solid tumors and immunosuppressive environments. This review aims to provide a comprehensive and detailed overview of the direct role of engineered exosomes as drug delivery systems and their immunomodulatory effects on tumors as an indirect approach to fighting cancer. Additionally, it will discuss novel immunotherapy options.

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world. Lamin B1 (LMNB1) is a key component of the nuclear skeleton structure. Recent studies have found that LMNB1 is overexpressed in tumor tissues and is associated with the prognosis of patients. However, the underlying mechanism remains unclear in HCC.

This study aims to explore the clinical significance and molecular mechanisms of LMNB1 in HCC.

The expression level of LMNB1 and its clinical values were analyzed with public databases, and the level of LMNB1 in HCC tissues and adjacent normal tissues was confirmed by qRT-PCR and IHC. Functional assays were conducted to explore the impact of LMNB1 knockdown on cell proliferation both in vivo and in vitro. Additionally, Genes and Genomes enrichment analysis, recovery analysis, and ChIP assays were employed to investigate its underlying molecular mechanisms. Finally, we carried out an analysis of the relationship between LMNB1 and immune cell infiltration in HCC.

LMNB1 was found to be overexpressed in HCC and correlated with the pathological stage and unfavorable prognosis. Functional assays demonstrated that LMNB1 promotes HCC proliferation both in vitro and in vivo. Further analysis revealed that LMNB1 promotes the progression of HCC by regulating CDKN1A expression. Furthermore, the infiltration of immune cells in HCC tissues suggests a potential correlation between immune infiltration cell markers and the expression of LMNB1.

LMNB1 emerged as a promising therapeutic target and prognostic biomarker for HCC, with its expression showing a correlation with several immune infiltration cell markers.

Mesenchymal stem cells (MSCs) have shown a great potential role in treating liver injury. MSCs can promote liver regeneration by differentiating into hepatocytes, and can also secrete exosomes to participate in the repair of liver injury. Increasing evidence has shown that mesenchymal stem cell-derived exosomes (MSC-EXOs) play an important role in treating liver injury. In this review, the biogenesis and function of exosomes and the characteristics of MSC-EXOs were analyzed based on recent research results. MSC-EXOs are significant in liver injuries such as liver fibrosis, liver failure, hepatocellular carcinoma, oxidative stress, and lipid steatosis, and participate in the process of liver regeneration.

The tumor microenvironment (TME) significantly influences cancer progression, and mesenchymal stem cells (MSCs) play a crucial role in interacting with tumor cells via paracrine signaling, affecting behaviors such as proliferation, migration, and epithelial-mesenchymal transition. While conventional 2D culture models have provided valuable insights, they cannot fully replicate the complexity and diversity of the TME. Therefore, developing 3D culture systems that better mimic in vivo conditions is essential. This review delves into the heterogeneous nature of the TME, spotlighting MSC-tumor cellular signaling and advancements in 3D culture technologies. Utilizing MSCs in cancer therapy presents opportunities to enhance treatment effectiveness and overcome resistance mechanisms. Understanding MSC interactions within the TME and leveraging 3D culture models can advance novel cancer therapies and improve clinical outcomes. Additionally, this review underscores the therapeutic potential of engineered MSCs, emphasizing their role in targeted anti-cancer treatments.

Drug resistance is a major challenge in cancer therapy that often leads to treatment failure and disease relapse. Despite advancements in chemotherapeutic agents and targeted therapies, cancers often develop drug resistance, making these treatments ineffective. Extracellular vesicles (EVs) have gained attention for their potential applications in drug delivery because of their natural origin, biocompatibility, and ability to cross biological barriers. Using the unique properties of EVs could enhance drug accumulation at target sites, minimize systemic toxicity, and precisely target specific cells. Here, we discuss the characteristics and functionalization of EVs, the mechanisms of drug resistance, and the applications of engineered EVs to overcome drug resistance. This review provides a comprehensive overview of the advancements in EV-based drug delivery systems and their applications in overcoming cancer drug resistance. We highlight the potential of EV-based drug delivery systems to revolutionize cancer therapy and offer promising strategies for more effective treatment modalities.

Traditional therapeutic approaches in the treatment of cancer have many side effects and are often ineffective and non-specific, leading to the development of therapy-resistant tumour cells. Recently, numerous discoveries about stem cells have given a new outlook on their application in oncology. Stem cells are unique because of their biological attributes, including self-renewal, differentiation in different types of specialized cells and synthesis of molecules that interplay with tumour niche. They are already used as an effective therapeutic option for haematological malignancies, such as multiple myeloma and leukaemia. The main goal of this study is to investigate the possible applications of different types of stem cells in cancer treatment and to summarize novel advances, as well as the limitations of their application in cancer treatment. Research and clinical trials that are underway revealed and confirmed the enormous potential of regenerative medicine in the treatment of cancer, especially when combined with different nanomaterials. Nanoengineering of stem cells has been the focus of novel studies in the area of regenerative medicine, such as the production of nanoshells and nanocarriers that enhance the transport and uptake of stem cells in their targeted tumour niche and enable the effective monitoring of stem cell effects on tumour cells. Although nanotechnology has a lot of limitations, it provides new opportunities for the development of effective and innovative stem cell therapies.

Extracellular vesicles (EVs) are bilayer vesicles released by cells in the microenvironment of the liver including parenchymal and non-parenchymal cells. They are the third important mechanism in the communications between cells, besides the secretion of cytokines and chemokines and the direct cell-to-cell contact. The aim of this review is to discuss the important role of EVs in viral liver disease, as there is increasing evidence that the transportation of viral proteins, all types of RNA, and viral particles including complete virions is implicated in the pathogenesis of both viral cirrhosis and viral-related hepatocellular carcinoma. The biogenesis of EVs is discussed and their role in the pathogenesis of viral liver diseases is presented. Their use as diagnostic and prognostic biomarkers is also analyzed. Most importantly, the significance of possible novel treatment strategies for liver fibrosis and hepatocellular carcinoma is presented, although available data are based on experimental evidence and clinical trials have not been reported.

Ribosomal proteins (RPs) are essential components of ribosomes, playing a role not only in ribosome biosynthesis, but also in various extra-ribosomal functions, some of which are implicated in the development of different types of tumors. As universally acknowledged, hepatocellular carcinoma (HCC) has been garnering global attention due to its complex pathogenesis and challenging treatments. In this review, we analyze the biological characteristics of RPs and emphasize their essential roles in HCC. In addition to regulating related signaling pathways such as the p53 pathway, RPs also act in proliferation and metastasis by influencing cell cycle, apoptosis, angiogenesis, and epithelial-to-mesenchymal transition in HCC. RPs are expected to unfold new possibilities for precise diagnosis and individualized treatment of HCC.

Hepatocellular carcinoma (HCC) stands as the sixth most prevalent cancer and the third leading cause of cancer mortality globally. Despite surgical resection being the preferred approach for early-stage HCC, most patients are diagnosed at intermediate to advanced stages, limiting treatment options to chemotherapy and immunotherapy, which often yield poor outcomes. Extracellular vesicles (EVs), minute lipid-bilayered particles released by diverse cells under various physiological and pathological conditions, are crucial for mediating communication between cells. Mounting evidence indicates that EVs sourced from different cells can profoundly influence the HCC tumor microenvironment (TME), thereby affecting the progression of HCC. Given their immunogenicity and liver-targeting properties, these EVs not only hold promise for HCC treatment but also provide avenues for advancing early diagnostic methods and assessing prognosis. This review not only describes the function of EVs within the HCC tumor microenvironment but also analyzes their therapeutic advantages and explores their significance in various therapeutic approaches for HCC, including chemotherapy, immunotherapy, combination therapy, and their role as innovative drug delivery carriers. Furthermore, it highlights the potential of EVs as biomarkers for the diagnosis and prognosis of HCC.

Liver cancer is one of the aggressive primary tumors as evident by high rate of incidence and mortality. Conventional treatments (e.g. chemotherapy) suffer from various drawbacks including wide drug distribution, low localized drug concentration, and severe off-site toxicity. Therefore, they cannot satisfy the mounting need for safe and efficient cancer therapeutics, and alternative novel strategies are needed. Nano-based drug delivery systems (NDDSs) are among these novel approaches that can improve the overall therapeutic outcomes. NDDSs are designed to encapsulate drug molecules and target them specifically to liver cancer. Thus, NDDSs can selectively deliver therapeutic agents to the tumor cells and avoid distribution to off-target sites which should improve the safety profile of the active agents. Nonetheless, NDDSs should be well designed, in terms of the preparing materials, nanocarriers structure, and the targeting strategy, in order to accomplish these objectives. This review discusses the latest advances of NDDSs for cancer therapy with emphasis on the aforementioned essential design components. The review also entails the challenges associated with the clinical translation of NDDSs, and the future perspectives towards next-generation NDDSs.

Radiation-induced lung injury (RILI) is associated with alveolar epithelial cell death and secondary fibrosis in injured lung. Mesenchymal stem cell (MSC)-derived exosomes have regenerative effect against lung injury and the potential to intervene of RILI. However, their intervention efficacy is limited because they lack lung targeting characters and do not carry sufficient specific effectors. SARS-CoV-2 spike glycoprotein (SARS-CoV-2-S-RBD) binds angiotensin-converting enzyme 2 (ACE2) receptor and mediates interaction with host cells. MiR-486-5p is a multifunctional miRNA with angiogenic and antifibrotic potential and acts as an effector in MSC-derived exosomes. Ferroptosis is a form of cell death associated with radiation injury, its roles and mechanisms in RILI remain unclear. In this study, we developed an engineered MSC-derived exosomes with SARS-CoV-2-S-RBD- and miR-486-5p- modification and investigated their intervention effects on RIPF and action mechanisms via suppression of epithelial cell ferroptosis.

Adenovirus-mediated gene modification led to miR-486-5p overexpression in human umbilical cord MSC exosomes (p < 0.05), thereby constructing miR-486-5p engineered MSC exosomes (miR-486-MSC-Exo). MiR-486-MSC-Exo promoted the proliferation and migration of irradiated mouse lung epithelial (MLE-12) cells in vitro and inhibited RILI in vivo (all p < 0.05). MiR-486-MSC-Exo suppressed ferroptosis in MLE-12 cells, and an in vitro assay revealed that the expression of fibrosis-related genes is up-regulated following ferroptosis (both p < 0.05). MiR-486-MSC-Exo reversed the up-regulated expression of fibrosis-related genes induced by TGF-β1 in vitro and improved pathological fibrosis in RIPF mice in vivo (all p < 0.05). SARS-CoV-2-S-RBD-modified and miR-486-5p-engineered MSC exosomes (miR-486-RBD-MSC-Exo) were also constructed, and the distribution of DiR dye-labeled miR-486-RBD-MSC-Exo in hACE2CKI/CKI Sftpc-Cre+ mice demonstrated long-term retention in the lung (p < 0.05). MiR-486-RBD-MSC-Exo significantly improved the survival rate and pathological changes in hACE2CKI/CKI Sftpc-Cre+ RIPF mice (all p < 0.05). Furthermore, miR-486-MSC-Exo exerted anti-fibrotic effects via targeted SMAD2 inhibition and Akt phosphorylation activation (p < 0.05).

Engineered MSC exosomes with SARS-CoV-2-S-RBD- and miR-486-5p-modification were developed. MiR-486-RBD-MSC-Exo suppressed ferroptosis and fibrosis of MLE-12 cells in vitro, and alleviated RILI and long-term RIPF in ACE2 humanized mice in vivo. MiR-486-MSC-Exo exerted anti-fibrotic effects via SMAD2 inhibition and Akt activation. This study provides a potential approach for RIPF intervention.

The tumor stroma plays a crucial role in tumor progression, and the interactions between the extracellular matrix, tumor cells, and stromal cells collectively influence tumor progression and the efficacy of therapeutic agents. Currently, utilizing components of the tumor stroma for drug delivery is a noteworthy strategy. A number of targeted drug delivery systems designed based on tumor stromal components are entering clinical trials. Therefore, this paper provides a thorough examination of the function of tumor stroma in the advancement of targeted drug delivery systems. One approach is to use tumor stromal components for targeted drug delivery, which includes certain stromal components possessing inherent targeting capabilities like HA, laminin, along with targeting stromal cells homologously. Another method entails directly focusing on tumor stromal components to reshape the tumor stroma and facilitate drug delivery. These drug delivery systems exhibit great potential in more effective cancer therapy strategies, such as precise targeting, enhanced penetration, improved safety profile, and biocompatibility. Ultimately, the deployment of these drug delivery systems can deepen our comprehension of tumor stroma and the advanced development of corresponding drug delivery systems.

Mesenchymal stem cells (MSCs) are capable of differentiating into various cell types and play a crucial role in repairing aging tissues and diseased organs. Aging manifests as a gradual loss of cellular, tissue, and organ function, leading to the progression of pathologies. Exosomes (Exos) are extracellular vesicles secreted by cells, which maintain cellular homeostasis, clear cellular debris, and facilitate communication between cells and organs. This review provides a comprehensive summary of the mechanisms for the synthesis and sorting of MSC-Exo miRNAs and summarizes the current research status of MSCs-Exos in mitigating aging and age-related diseases. It delves into the underlying molecular mechanisms, which encompass antioxidative stress, anti-inflammatory response, and the promotion of angiogenesis. Additionally, this review also discusses potential challenges in and future strategies for advancing MSC-Exo miRNA-based therapies in the treatment of aging and age-related diseases.

Exosomes are nanoscale membrane bound vesicles secreted by almost all types of cells. Their unique attributes, such as minimal immunogenicity and compatibility with biological systems, make them novel carriers for drug delivery. These native exosomes harbor proteins, nucleic acids, small molecule compounds, and fluorogenic agents. Moreover, through a combination of chemical and bioengineering methodologies, exosomes are tailored to transport precise therapeutic payloads to designated cells or tissues. In this review, we summarize the strategies for exosome modification and drug loading modalities in engineered exosomes. In addition, we provide an overview of the advances in the use of engineered exosomes for targeted drug delivery. Lastly, we discuss the merits and limitations of chemically engineered versus bioengineered exosome-mediated target therapies. These insights offer additional options for refining engineered exosomes in pharmaceutical development and hold promise for expediting the successful translation of engineered exosomes from the bench to the bedside.

The insufficient and unspecific target of classical chemotherapies often leads to therapy resistance and cancer recurrence. Over the past decades, discoveries about mesenchymal stem cell (MSC) biology have provided new potential approaches to improve cancer therapy. Researchers have utilised the multipotent, regenerative and immunosuppressive qualities of MSCs and tropisms towards inflammatory, hypoxic and malignant sites in various therapeutic applications. Although MSC-based therapies have generally been demonstrated safe, their effectiveness remains limited when these cells are used alone. However, through genetic engineering, researchers have proven that MSCs can be modified to have specialised delivery roles to increase their therapeutic efficacy in cancer treatment. They can be made to overexpress therapeutic proteins through viral or non-viral genetic modification, which enhances their innate properties. Nevertheless, these engineering strategies must be optimised to increase therapeutic efficacy and targeting effectiveness while minimising any loss of MSC function. This review underscores the cutting-edge methods for engineering MSCs, discusses their promise and the difficulties in translating them into clinical settings, and offers some prospective suggestions for the future on achieving their full therapeutic potential.

Extracellular vesicles (EVs)-based intercellular communication (through exosomes, microvesicles, and apoptotic bodies) is conserved across all kingdoms of life. In recent years, exosomes have gained much attention for targeted pharmaceutical administration due to their unique features, nanoscale size, and capacity to significantly contribute to cellular communication. As drug delivery vehicles, exosomes have several advantages over alternative nanoparticulate drug delivery technologies. A key advantage lies in their comparable makeup to the body's cells, which makes them non-immunogenic. However, exosomes vesicles face several challenges, including a lack of an effective and standard production technique, decreased drug loading capacity, limited characterization techniques, and underdeveloped isolation and purification procedures. Exosomes are well known for their long-term safety and natural ability to transport intercellular nucleic acids and medicinal compounds across the blood-brain-barrier (BBB). Therefore, in addition to revealing new insights into exosomes' distinctiveness, the growing availability of new analytical tools may drive the development of next-generation synthetic systems. Herein, light is shed on exosomes as drug delivery vehicles in anti-infective therapy by reviewing the literature on primary articles published between 2002 and 2023. Additionally, the benefits and limitations of employing exosomes as vehicles for therapeutic drug delivery are also discussed.

Solid tumors cause 90% of cancers and remain the primary cause of mortality. However, treating solid tumors presents significant challenges due to the complex tumor microenvironment and drug resistance, leading to inadequate treatment targeting and severe side effects. Surgery, radiotherapy, and chemotherapy Although it is an effective method for the treatment of solid tumors, it can lead to organ dysfunction and affect patient prognosis. Therefore, it is imperative to improve treatment precision and organ repair capabilities to manage solid tumors. Mesenchymal stem cell extracellular vesicles (MSC-EVs) have wide application prospects as a new agent for solid tumor therapy. Firstly, MSC-EVs is a derivative of MSCs. It has the function of promoting tissue regeneration by inducing dedifferentiation in surviving cells after injury. Additionally, MSC-EVs offer unique advantages in terms of safety, stability and penetrability, making them a promising extracellular therapeutic modality for solid tumor treatment. Finally, MSC-EVs are able to enhance therapeutic efficacy through engineering strategies. To sum up, this review takes MSC-EVs as its object. And then we discuss recent advancements and engineering strategies in the use of MSC-EVs for soid tumor suppression. This review aims to inspire researchers to devise a new method for effectively treat solid tumors.

Ticks are important blood feeding ectoparasites that transmit pathogens to wildlife, domestic animals, and humans. Hard ticks can feed for several days to weeks, nevertheless they often go undetected. This phenomenon can be explained by a tick's ability to release analgesics, immunosuppressives, anticoagulants, and vasodilators within their saliva. Several studies have identified extracellular vesicles (EVs) as carriers of some of these effector molecules. Further, EVs, and their contents, enhance pathogen transmission, modulate immune responses, and delay wound healing. EVs are double lipid-membrane vesicles that transport intracellular cargo, including microRNAs (miRNAs) to recipient cells. miRNAs are involved in regulating gene expression post-transcriptionally. Interestingly, tick-derived miRNAs have been shown to enhance pathogen transmission and affect vital biological processes such as oviposition, blood digestion, and molting. miRNAs have been found within tick salivary EVs. This review focuses on current knowledge of miRNA loading into EVs and homologies reported in ticks. We also describe findings in tick miRNA profiles, including miRNAs packed within tick salivary EVs. Although no functional studies have been done to investigate the role of EV-derived miRNAs in tick feeding, we discuss the functional characterization of miRNAs in tick biology and pathogen transmission. Lastly, we propose the possible uses of tick miRNAs to develop management tools for tick control and to prevent pathogen transmission. The identification and functional characterization of conserved and tick-specific salivary miRNAs targeting important molecular and immunological pathways within the host could lead to the discovery of new therapeutics for the treatment of tick-borne and non-tick-borne human diseases.

Exosomes, minute vesicles ubiquitously released by diverse cell types, serve as critical mediators in intercellular communication. Their pathophysiological relevance, especially in malignancies, has garnered significant attention. A meticulous exploration of the exosomal impact on cancer development has unveiled avenues for innovative and clinically valuable techniques. The cargo conveyed by exosomes exerts transformative effects on both local and distant microenvironments, thereby influencing a broad spectrum of biological responses in recipient cells. These membrane-bound extracellular vesicles (EVs) play a pivotal role in delivering bioactive molecules among cells and organs. Cellular and biological processes in recipient cells, ranging from stromal cell reprogramming to immunological responses, extracellular matrix formation, and modulation of cancer cell activation, expansion, and metastasis, are subject to exosome-mediated cell-to-cell communication. Moreover, exosomes have been implicated in endowing cancer cells with resistance to treatment. Extensive research has explored the potential of exosomes as therapeutic targets and diagnostic indicators. This comprehensive review seeks to provide an in-depth understanding of the pivotal components and roles of exosomes in tumorigenesis, growth, progression, and therapeutic responses. The insights into the multifaceted involvement of exosomes in malignant cancers are essential for the scientific community, fostering the development of novel therapeutic and diagnostic strategies in the relentless pursuit of cancer.

Adipose tissue (AT) serves as an energy-capacitive organ and performs functions involving paracrine- and endocrine-mediated regulation via extracellular vesicles (EVs) secretion. Exosomes, a subtype of EVs, contain various bioactive molecules with regulatory effects, such as nucleic acids, proteins, and lipids. AT-derived exosomes (AT-exos) include exosomes derived from various cells in AT, including adipocytes, adipose-derived stem cells (ADSCs), macrophages, and endothelial cells. This review aimed to comprehensively evaluate the impacts of different AT-exos on the regulation of physiological and pathological processes. The contents and functions of adipocyte-derived exosomes and ADSC-derived exosomes are compared simultaneously, highlighting their similarities and differences. The contents of AT-exos have been shown to exert complex regulatory effects on local inflammation, tumor dynamics, and insulin resistance. Significantly, differences in the cargoes of AT-exos have been observed among diabetes patients, obese individuals, and healthy individuals. These differences could be used to predict the development of diabetes mellitus and as therapeutic targets for improving insulin sensitivity and glucose tolerance. However, further research is needed to elucidate the underlying mechanisms and potential applications of AT-exos.

Mesenchymal stem/stromal cells (MSCs) have the capacity to migrate to tumor sites in vivo and transmit paracrine signals by secreting extracellular vesicles (EVs) to regulate tumor biological behaviors. MSC-derived EVs (MSC-EVs) have similar tumor tropism and pro- or anti-tumorigenesis as their parental cells and exhibit superior properties in drug delivery. MSC-EVs can transfer microRNAs (miRNAs) to tumor cells, thereby manipulating multiple key cancer-related pathways, and further playing a vital role in the tumor growth, metastasis, drug resistance and other aspects. In addition, tumor cells can also influence the behaviors of MSCs in the tumor microenvironment (TME), orchestrating this regulatory process via miRNAs in EVs (EV-miRNAs). Clarifying the specific mechanism by which MSC-derived EV-miRNAs regulate tumor progression, as well as investigating the roles of EV-miRNAs in the TME will contribute to their applications in tumor pharmacotherapy. This article mainly reviews the multifaceted roles and mechanism of miRNAs in MSC-EVs affecting tumor progression, the crosstalk between MSCs and tumor cells caused by EV-miRNAs in the TME. Eventually, the clinical applications of miRNAs in MSC-EVs in tumor therapeutics are illustrated.

In the fields of tissue engineering and regenerative medicine, extracellular vesicles (EVs) have become viable therapeutic tools. EVs produced from stem cells promote tissue healing by regulating the immune system, enhancing cell proliferation and aiding remodeling processes. Recently, EV has gained significant attention from researchers due to its ability to treat various diseases. Unlike stem cells, stem cell-derived EVs show lower immunogenicity, are less able to overcome biological barriers, and have a higher safety profile. This makes the use of EVs derived from cell-free stem cells a promising alternative to whole-cell therapy. This review focuses on the biogenesis, isolation, and characterization of EVs and highlights their therapeutic potential for bone fracture healing, wound healing, and neuronal tissue repair and treatment of kidney and intestinal diseases. Additionally, this review discusses the potential of EVs for the treatment of cancer, COVID-19, and HIV. In summary, the use of EVs derived from stem cells offers a new horizon for applications in tissue engineering and regenerative medicine.

Mesenchymal stem cells (MSCs) are recruited by malignant tumor cells to the tumor microenvironment (TME) and play a crucial role in the initiation and progression of malignant tumors. This role encompasses immune evasion, promotion of angiogenesis, stimulation of cancer cell proliferation, correlation with cancer stem cells, multilineage differentiation within the TME, and development of treatment resistance. Simultaneously, extensive research is exploring the homing effect of MSCs and MSC-derived extracellular vesicles (MSCs-EVs) in tumors, aiming to design them as carriers for antitumor substances. These substances are targeted to deliver antitumor drugs to enhance drug efficacy while reducing drug toxicity. This paper provides a review of the supportive role of MSCs in tumor progression and the associated molecular mechanisms. Additionally, we summarize the latest therapeutic strategies involving engineered MSCs and MSCs-EVs in cancer treatment, including their utilization as carriers for gene therapeutic agents, chemotherapeutics, and oncolytic viruses. We also discuss the distribution and clearance of MSCs and MSCs-EVs upon entry into the body to elucidate the potential of targeted therapies based on MSCs and MSCs-EVs in cancer treatment, along with the challenges they face.

Cancer cachexia is a complex metabolic syndrome characterized by unintentional loss of skeletal muscle and body fat. This syndrome is frequently associated with different types of cancer and negatively affects the prognosis and outcome of these patients. It involves a dynamic interplay between tumor cells and adipose tissue, where tumor-derived extracellular vesicles (EVs) play a crucial role in mediating intercellular communication. Tumor cells release EVs containing bioactive molecules such as hormones (adrenomedullin, PTHrP), pro-inflammatory cytokines (IL-6), and miRNAs (miR-1304-3p, miR-204-5p, miR-155, miR-425-3p, miR-146b-5p, miR-92a-3p), which can trigger lipolysis and induce the browning of white adipocytes contributing to a cancer cachexia phenotype. On the other hand, adipocyte-derived EVs can reprogram the metabolism of tumor cells by transporting fatty acids and enzymes involved in fatty acid oxidation, resulting in tumor growth and progression. These vesicles also carry leptin and key miRNAs (miR-155-5p, miR-10a-3p, miR-30a-3p, miR-32a/b, miR-21), thereby supporting tumor cell proliferation, metastasis formation, and therapy resistance. Understanding the intricate network underlying EV-mediated communication between tumor cells and adipocytes can provide critical insights into the mechanisms driving cancer cachexia. This review consolidates current knowledge on the crosstalk between tumor cells and adipose tissue mediated by EVs and offers valuable insights for future research. It also addresses controversial topics in the field and possible therapeutic approaches to manage cancer cachexia and ultimately improve patient outcomes and quality of life.

Hepatocellular carcinoma (HCC) ranks as the most prevalent of primary liver cancers and stands as the third leading cause of cancer-related deaths. Early-stage HCC can be effectively managed with available treatment modalities ranging from invasive techniques, such as liver resection and thermoablation, to systemic therapies primarily employing tyrosine kinase inhibitors. Unfortunately, these interventions take a significant toll on the body, either through physical trauma or the adverse effects of pharmacotherapy. Consequently, there is an understandable drive to develop novel HCC therapies. Adipose-derived stem cells (ADSCs) are a promising therapeutic tool. Their facile extraction process, coupled with the distinctive immunomodulatory capabilities of their secretome, make them an intriguing subject for investigation in both oncology and regenerative medicine. The factors they produce are both enzymes affecting the extracellular matrix (specifically, metalloproteinases and their inhibitors) as well as cytokines and growth factors affecting cell proliferation and invasiveness. So far, the interactions observed with various cancer cell types have not led to clear conclusions. The evidence shows both inhibitory and stimulatory effects on tumor growth. Notably, these effects appear to be dependent on the tumor type, prompting speculation regarding their potential inhibitory impact on HCC. This review briefly synthesizes findings from preclinical and clinical studies examining the effects of ADSCs on cancers, with a specific focus on HCC, and emphasizes the need for further research.

Exosomes, also termed extracellular vesicles (EVs), are an important component of the tumor microenvironment (TME) and exert versatile effects on the molecular communications in the TME of hepatocellular carcinoma (HCC). Exosome-mediated intercellular communication is closely associated with the tumorigenesis and development of HCC. Exosomes can be extracted through ultracentrifugation and size exclusion, followed by molecular analysis through sequencing. Increasing studies have confirmed the important roles of exosome-derived ncRNAs in HCC, including tumorigenesis, progression, immune escape, and treatment resistance. Due to the protective membrane structure of exosomes, the ncRNAs carried by exosomes can evade degradation by enzymes in body fluids and maintain good expression stability. Thus, exosome-derived ncRNAs are highly suitable as biomarkers for the diagnosis and prognostic prediction of HCC, such as exosomal miR-21-5p, miR-221-3p and lncRNA-ATB. In addition, substantial studies revealed that the up-or down-regulation of exosome-derived ncRNAs had an important impact on HCC progression and response to treatment. Exosomal biomarkers, such as miR-23a, lncRNA DLX6-AS1, miR-21-5p, lncRNA TUC339, lncRNA HMMR-AS1 and hsa_circ_0004658, can reshape immune microenvironment by regulating M2-type macrophage polarization and then promote HCC development. Therefore, by controlling exosome biogenesis and modulating exosomal ncRNA levels, HCC may be inhibited or eliminated. In this current review, we summarized the recent findings on the role of exosomes in HCC progression and analyzed the relationship between exosome-derived ncRNAs and HCC diagnosis and treatment.

Wound healing in diabetic patients is frequently hampered. Adipose-derived stem cell exosomes (ADSC-eoxs), serving as a crucial mode of intercellular communication, exhibit promising therapeutic roles in facilitating wound healing. This review aims to comprehensively outline the molecular mechanisms through which ADSC-eoxs enhance diabetic wound healing. We emphasize the biologically active molecules released by these exosomes and their involvement in signaling pathways associated with inflammation modulation, cellular proliferation, vascular neogenesis, and other pertinent processes. Additionally, the clinical application prospects of the reported ADSC-eoxs are also deliberated. A thorough understanding of these molecular mechanisms and potential applications is anticipated to furnish a theoretical groundwork for combating diabetic wound healing.

Prostate cancer represents the second most prevalent form of cancer found in males, and stands as the fifth primary contributor to cancer-induced mortality on a global scale. Research has shown that transplanted mesenchymal stem cells (MSCs) can migrate by homing to tumor sites in the body. In prostate cancer, researchers have explored the fact that MSC-based therapies (including genetically modified delivery vehicles or vectors) and MSC-derived exosomes are emerging as attractive options to improve the efficacy and safety of traditional cancer therapies. In addition, researchers have reported new insights into the application of extracellular vesicle (EV)-MSC therapy as a novel treatment option that could provide a more effective and targeted approach to prostate cancer treatment. Moreover, the new generation of exosomes, which contain biologically functional molecules as signal transducers between cells, can simultaneously deliver different therapeutic agents and induce an anti-tumor phenotype in immune cells and their recruitment to the tumor site. The results of the current research on the use of MSCs in the treatment of prostate cancer may be helpful to researchers and clinicians working in this field. Nevertheless, it is crucial to emphasize that although dual-role MSCs show promise as a therapeutic modality for managing prostate cancer, further investigation is imperative to comprehensively grasp their safety and effectiveness. Ongoing clinical trials are being conducted to assess the viability of MSCs in the management of prostate cancer. The results of these trials will help determine the viability of this approach. Based on the current literature, engineered MSCs-EV offer great potential for application in targeted tumor therapy.

Extracellular vesicles (EVs) are small lipid bilayer-enclosed vesicles that mediate vital cellular communication by transferring cargo between cells. Among these, tissue-derived extracellular vesicles (Ti-EVs) stand out due to their origin from the tissue microenvironment, providing a more accurate reflection of changes in this setting. This unique advantage makes Ti-EVs valuable in investigating the intricate relationship between extracellular vesicles and cancer progression. Despite considerable research efforts exploring the association between Ti-EVs and cancers, a comprehensive clustering or grouping of these studies remains lacking. In this review, we aim to fill this gap by presenting a comprehensive synthesis of the mechanisms underlying Ti-EV generation, release, and transport within cancer tissues. Moreover, we delve into the pivotal roles that Ti-EVs play in cancer progression, shedding light on their potential as diagnostic and therapeutic tools. The review culminates in the construction of a comprehensive functional spectrum of Ti-EVs, providing a valuable reference for future research endeavors. By summarizing the current state of knowledge on Ti-EVs and their significance in tumor biology, this work contributes to a deeper understanding of cancer microenvironment dynamics and opens up avenues for harnessing Ti-EVs in diagnostic and therapeutic applications.