Macrophages are essential for the human body in both physiological and pathological conditions, engulfing undesirable substances and participating in several processes, such as organism growth, immune regulation, and maintenance of homeostasis. Macrophages play an important role in anti-bacterial and anti-tumoral responses. Aberrance in the phagocytosis of macrophages may lead to the development of several diseases, including tumors. Tumor cells can evade the phagocytosis of macrophages, and “educate” macrophages to become pro-tumoral, resulting in the reduced phagocytosis of macrophages. Hence, harnessing the phagocytosis of macrophages is an important approach to bolster the efficacy of anti-tumor treatment. In this review, we elucidated the underlying phagocytosis mechanisms, such as the equilibrium among phagocytic signals, receptors and their respective signaling pathways, macrophage activation, as well as mitochondrial fission. We also reviewed the recent progress in the area of application strategies on the basis of the phagocytosis mechanism, including strategies targeting the phagocytic signals, antibody-dependent cellular phagocytosis (ADCP), and macrophage activators. We also covered recent studies of Chimeric Antigen Receptor Macrophage (CAR-M)-based anti-tumor therapy. Furthermore, we summarized the shortcomings and future applications of each strategy and look into their prospects with the hope of providing future research directions for developing the application of macrophage phagocytosis-promoting therapy.

Macrophages, key players in the immune system, exhibit diverse roles in tumor progression and regulation. Macrophages release extracellular vesicles (EVs), membrane-bound particles that facilitate intercellular communication and cargo transfer. Macrophage-derived EVs (M-EVs) demonstrate a complex dual function in tumor development, with their effects dependent on their origin and the tumor microenvironment. M1-EVs show anti-tumor properties by reversing immune escape, while M2-EVs promote tumor biogenesis, invasion, metastasis, and therapeutic resistance. Tumor-associated macrophage-derived EVs (TAM-EVs) generally facilitate tumor progression but may exhibit anti-tumor characteristics in specific cancers. M-EVs, particularly M1-EVs, show promise as drug delivery vehicles in tumor-targeted therapy due to their targeting capabilities and ability to cross physiological barriers. Despite challenges in clinical application, ongoing research aims to harness the potential of M-EVs for more effective and personalized cancer treatments. This review summarizes how M-EVs influence tumor cell behavior, their mechanisms of action, and the challenges related to specificity, isolation, and clinical application. Collectively, this comprehensive analysis not only provides researchers with a better understanding of the complex roles of M-EVs in cancer biology but also lights the way for innovative therapeutic strategies, potentially advancing the development of more effective and personalized cancer treatments.

Ischemic stroke is a debilitating neurovascular condition characterized by a focal disruption of the cerebral blood supply. Current clinical interventions have been developed to restore the cerebral circulation; however, functional recovery from neurological injury remains unsatisfactory. Extracellular vesicles derived from mesenchymal stem cells are prominent therapeutic agents for neurological diseases. Notably, extracellular vesicles derived from dental stem cells (DSC-EVs) are considered promising because of their developmental similarity to the neural crest. In rat models of ischemic stroke, intranasally administered DSC-EVs exerted more significant therapeutic efficacy compared to extracellular vesicles derived from bone marrow and adipose tissue sources. This non-invasive intranasal route increased detectable brain-associated fluorescence without the need for systemic injections. Functionally, DSC-EVs improved neurological recovery by reducing infarct size and restoring blood–brain barrier integrity. Mechanistically, DSC-EVs, enriched in miR-21-5p, attenuated oxidative stress in cerebral microvascular endothelial cells, potentially involving the downregulation of S100A10 expression and thereby preserving tight junction integrity. Our findings reveal the distinguishing therapeutic potential of DSC-EVs in ischemic stroke and suggest a mechanism by which intranasally delivered DSC-EVs alleviate ischemia–reperfusion-induced blood–brain barrier disruption through the modulation of S100A10-associated endothelial oxidative stress, supporting further preclinical evaluation of DSC-EVs as a non-invasive approach for post-stroke neurovascular repair.