Extracellular vesicles (EVs), are membrane-bound vesicles that have many advantages over traditional nanocarriers for drug and gene delivery. Evidence from recent studies indicate that EVs have therapeutic capability with chemical or biological modification. Tumor-derived exosomes (TEXs) were used as a new type of antigens or tumor vaccines in anti-tumor immunotherapy. With superior characteristics, modified EVs were applied to loaded and delivered synthetic drugs, silencing RNA, and microRNA for treatment. Different surface functionalization strategies have been proposed to improve the therapeutic functions of EVs. Appropriately modified EVs for disease intervention provide new avenues for effective clinical treatment strategies. Therefore, this review aimed at elucidating the therapeutic functions of EVs to generate new ideas for treatment and to unlock their hidden potential in translational medicine.
Significant developments in cell therapy and biomaterial science have broadened the therapeutic landscape of tissue regeneration. Tissue damage is a complex biological process in which different types of cells play a specific role in repairing damaged tissues and growth factors strictly regulate the activity of these cells. Hydrogels have become promising biomaterials for tissue regeneration if appropriate materials are selected and the hydrogel properties are well-regulated. Importantly, they can be used as carriers for living cells and growth factors due to the high water-holding capacity, high permeability, and good biocompatibility of hydrogels. Cell-loaded hydrogels can play an essential role in treating damaged tissues and open new avenues for cell therapy. There is ample evidence substantiating the ability of hydrogels to facilitate the delivery of cells (stem cell, macrophage, chondrocyte, and osteoblast) and growth factors (bone morphogenetic protein, transforming growth factor, vascular endothelial growth factor and fibroblast growth factor). This paper reviewed the latest advances in hydrogels loaded with cells or growth factors to promote the reconstruction of tissues. Furthermore, we discussed the shortcomings of the application of hydrogels in tissue engineering to promote their further development.
Exosomes derived from tumor cells contain various molecular components, such as proteins, RNA, DNA, lipids, and carbohydrates. These components play a crucial role in all stages of tumorigenesis and development. Moreover, they reflect the physiological and pathological status of parental tumor cells. Recently, tumor-derived exosomes have become popular biomarkers for non-invasive liquid biopsy and the diagnosis of numerous cancers. The interdisciplinary significance of exosomes research has also attracted growing enthusiasm. However, the intrinsic nature of tumor-derived exosomes requires advanced methods to detect and evaluate the complex biofluid. This review analyzes the relationship between exosomes and tumors. It also summarizes the exosomal biological origin, composition, and application of molecular markers in clinical cancer diagnosis. Remarkably, this paper constitutes a comprehensive summary of the innovative research on numerous detection strategies for tumor-derived exosomes with the intent of providing a theoretical basis and reference for early diagnosis and clinical treatment of cancer.
Background: As sentinel cells of innate immunity, macrophages exhibit microenvironment-driven functional plasticity critical for immune regulation and tissue homeostasis, yet maladaptive metabolic reprogramming-induced polarization dysregulation exacerbates disease progression by manifesting immune dysfunction. Summary: This review systematically deciphers the metabolic signatures governing macrophage polarization – spanning amino acid metabolism, glycolytic flux, lipid dynamics, and iron homeostasis – while dissecting how pathological microenvironments (encompassing tumor niches, atherosclerotic plaques, and obese adipose tissue) co-opt these pathways to drive pathogenesis. Crucially, this analysis demonstrates that cellular metabolism dictates macrophage phenotypic/functional states across disease contexts, with comprehensive decoding of their metabolic networks emerging as imperative for developing next-generation immunotherapies. Key Messages: Therapeutically, pathogenic polarization may be reversed through strategic interventions targeting metabolite-sensing receptors, pharmacologically blocking metabolic checkpoints, and reprogramming core metabolic modalities to restore immunoregulatory competence.
Exosomes carry genetic information originating from their parental cells, raising their possibility as novel noninvasive biomarkers for cancer. Tumor-derived exosomes (TEXs) have a variety of endogenous cargos that reflect the pathophysiology status and information of tumor cells. TEXs are increasingly being recognized as potential biomarkers for cancer diagnosis prognosis, and monitoring. It is important to develop a variety of sensitive methods, including probes and biomaterials to isolate exosomes. A variety of approaches for detecting exosomes have been established. By combining exosome DNA and RNA sequencing tools, exosome proteomics analysis and immunoassay technology, it is expected that exosomes will gain widespread use in the diagnosis and treatment of cancer.
Macrophages play a critical role in the body's defense against cancer by phagocytosing tumor cells, presenting antigens, and activating adaptive T cells. However, macrophages are intrinsically incapable of delivering targeted cancer immunotherapies. Engineered adoptive cell therapy introduces new targeting and antitumor capabilities by modifying macrophages to enhance the innate immune response of cells and improve clinical efficacy. In this study, we developed engineered macrophage cholesterol-AS1411-M1 (CAM1) for cellular immunotherapy. To target macrophages, cholesterol-AS1411 aptamers were anchored to the surface of M1 macrophages to produce CAM1 without genetic modification or cell damage. CAM1 induced significantly higher apoptosis/mortality than unmodified M1 macrophages in murine breast cancer cells. Anchoring AS1411 on the surface of macrophages provided a novel approach to construct engineered macrophages for tumor immunotherapy.