Self‐Activatable Photo‐Extracellular Vesicle for Synergistic Trimodal Anticancer Therapy

Abstract

Extracellular vesicles (EVs) hold great potential in both disease treatment and drug delivery. However, accurate drug release from EVs, as well as the spontaneous treatment effect cooperation of EVs and drugs at target tissues, is still challenging. Here, an engineered self‐activatable photo‐EV for synergistic trimodal anticancer therapy is reported. M1 macrophage‐derived EVs (M1 EVs) are simultaneously loaded with bis[2,4,5‐trichloro‐6‐(pentyloxycarbonyl) phenyl] oxalate (CPPO), chlorin e6 (Ce6), and prodrug aldoxorubicin (Dox‐EMCH). After administration, the as‐prepared system actively targets tumor cells because of the tumor‐homing capability of M1 EVs, wherein M1 EVs repolarize M2 to M1 macrophages, which not only display immunotherapy effects but also produce H2O2. The reaction between H2O2 and CPPO generates chemical energy that activates Ce6, creating both chemiluminescence for imaging and singlet oxygen (1O2) for photodynamic therapy (PDT). Meanwhile, 1O2‐induced membrane rupture leads to the release of Dox‐EMCH, which is then activated and penetrates the deep hypoxic areas of tumors. The synergism of immunotherapy, PDT, and chemotherapy results in potent anticancer efficacy, showing great promise to fight cancers.

M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis

“…Several researches reported that M2 macrophage promoted the migration and invasion of ESCs, angiogenesis, and fibrosis in endometriosis ( 11 – 13 , 15 , 44 ). Previous studies have demonstrated the antitumor efficacy associated with switching from the M2 to the M1 phenotype ( 5 , 45 ). In this study, we confirmed that M1NVs could effectively reprogram M2 macrophages into M1 macrophages both in vitro and in vivo .…”

Uptake of oxidative stress-mediated extracellular vesicles by vascular endothelial cells under low magnitude shear stress

“…Extracellular vesicles (EVs) are nanosized membranous vesicles produced by most kinds of cells [ 14 ]. They are enclosed by a lipid bilayer that surrounds an aqueous core containing proteins, lipids, and nucleic acids [ 15 ].…”

Polyvalent spherical aptamer engineered macrophages: X-ray-actuated phenotypic transformation for tumor immunotherapy

“…Compared with unpolarized macrophages, M1 cells can produce nitric oxide (NO), interleukin-12 (IL-12) and other cytokines to exert effective anticancer effects. 42,43 Thus, we first measured NO generation using a luminescent probe. 44 After macrophages were subjected to different treatments for 12 h, the culture medium in the different groups was collected and centrifuged.…”