Macrophage-Derived Extracellular Vesicles: A Promising Tool for Personalized Cancer Therapy

Abstract

The incidence of cancer is increasing dramatically, affecting all ages of the population and reaching an ever higher worldwide mortality rate. The lack of therapies’ efficacy is due to several factors such as a delay in diagnosis, tumor regrowth after surgical resection and the occurrence of multidrug resistance (MDR). Tumor-associated immune cells and the tumor microenvironment (TME) deeply affect the tumor’s progression, leading to several physicochemical changes compared to physiological conditions. In this scenario, macrophages play a crucial role, participating both in tumor suppression or progression based on the polarization of onco-suppressive M1 or pro-oncogenic M2 phenotypes. Moreover, much evidence supports the pivotal role of macrophage-derived extracellular vesicles (EVs) as mediators in TME, because of their ability to shuttle the cell–cell and organ–cell communications, by delivering nucleic acids and proteins. EVs are lipid-based nanosystems with a broad size range distribution, which reflect a similar composition of native parent cells, thus providing a natural selectivity towards target sites. In this review, we discuss the impact of macrophage-derived EVs in the cancer’s fate as well as their potential implications for the development of personalized anticancer nanomedicine.

Cancer signaling, cell/gene therapy, diagnosis and role of nanobiomaterials

“…The therapeutic potential of immunity cell-derived nanomedicine, specifically macrophage-derived nanomedicine, has been shown by recent studies. Since these nanovesicles originate from immune system cells that readily recognize and kill tumor cells, they have inherent long-circulation qualities and a natural affinity for cancer tissues (Barone et al, 2022;Yan et al, 2023).…”

Recent advances in therapeutic engineered extracellular vesicles

“…21,33 Furthermore, macrophage-derived EVs may contain inflammatory mediators such as cytokines and chemokines, regulating local immune responses and inflammation. 34 Dendritic cell-derived EVs play crucial roles in immune tolerance and suppression by promoting regulatory T cell differentiation and suppressing effector T cell responses. 35…”

Exosomes as Anticancer Drug Delivery Vehicles: Prospects and Challenges

“…Specific cell-derived exosomes exhibit a natural tropism for the cancer microenvironment, which is critical for improving the targeting properties of nanomedicines [150]. Macrophage-derived exosomes, for example, can target cancer cells through their surface-expressed LFA-1 protein and ICAM-1 that is overexpressed in most cancer cells [97].…”