Iron Oxide Nanoparticles Engineered Macrophage-Derived Exosomes for Targeted Pathological Angiogenesis Therapy

Abstract

Engineering exosomes with nanomaterials usually leads to the damage of exosomal membrane and bioactive molecules. Here, pathological angiogenesis targeting exosomes with magnetic imaging, ferroptosis inducing, and immunotherapeutic properties is fabricated using a simple coincubation method with macrophages being the bioreactor. Extremely small iron oxide nanoparticle (ESIONPs) incorporated exosomes (ESIONPs@EXO) are acquired by sorting the secreted exosomes from M1-polarized macrophages induced by ESIONPs. ESIONPs@EXO suppress pathological angiogenesis in vitro and in vivo without toxicity. Furthermore, ESIONPs@EXO target pathological angiogenesis and exhibit an excellent T1-weighted contrast property for magnetic resonance imaging. Mechanistically, ESIONPs@EXO induce ferroptosis and exhibit immunotherapeutic ability toward pathological angiogenesis. These findings demonstrate that a pure biological method engineered ESIONPs@EXO using macrophages shows potential for targeted pathological angiogenesis therapy.

Magnetic particle imaging reveals that iron-labeled extracellular vesicles accumulate in brains of mice with metastases

“…In addition to their ability to cross the BBB, EV use is favorable because of low immunogenicity, biodegradability, and their non-toxic nature. Further, they can carry cargo, such as iron particles in this study and others 24,26,28,31,32,52,53 , as well as therapeutics 17,18,[20][21][22][23]25,50,51 . The mechanisms in which EVs cross the BBB is not fully understood; however, some possible routes which have been explored are micropinocytosis, clathrin-dependent endocytosis and caveolae-dependent endocytosis 15,16,54,55 .…”

“…Iron-labeled EVs have been imaged previously using MRI [25][26][27]30,31 and MPI 32 . Methods used to label EVs have been through direct labeling, or indirect labeling where the parental cell is co-incubated with the iron and is allowed to take up the nanoparAcle.…”

“…Because EVs can circulate in the bloodstream for a prolonged period of Ame, can cross the BBB 12,13,[15][16][17][18][19][20] , and are manipulable as carriers of drugs, nucleic acids, or nanoparAcles [17][18][19][20][21][22][23][24][25][26][27][28][29] , there is vast potenAal to engineer EVs as imaging or delivery tools to target brain metastases. Previous studies have labeled EVs with superparamagneAc iron oxide (SPIO) nanoparAcles for in vivo tracking using magneAc resonance imaging (MRI) [24][25][26]30,31 and to a lesser extent, magneAc parAcle imaging (MPI) 32 . AddiAonally, EVs derived from tumor cells have been shown to improve delivery to parental tumor cells in vivo [33][34][35] .…”

Reprogramming Tumor-Associated Macrophage Using Nanocarriers: New Perspectives to Halt Cancer Progression

“…In another study [99], exosomes derived from macrophages were electroporated with extremely small iron oxide nanoparticles (ESIONPs@EXO) which induce ferroptosis. It was shown that treatment with ESIONPs@EXO resulted in M2 to M1 reprogramming, significantly inhibited vessel formation, reduced endothelial cell sprouting, and suppressed pathological angiogenesis in vivo via VEGF-independent mechanism in the ocular melanoma model, also prohibiting tumor cell proliferation and migration.…”

Magnetic Particle Imaging Reveals that Iron-Labeled Extracellular Vesicles Accumulate in Brains of Mice with Metastases

“…Because EVs can circulate in the bloodstream for a prolonged period of time, can cross the BBB, ,,− and can be manipulated as carriers of drugs, nucleic acids, or nanoparticles, − there is vast potential to engineer EVs as imaging or delivery tools to target brain metastases. Previous studies have labeled EVs with superparamagnetic iron oxide (SPIO) nanoparticles for in vivo tracking using magnetic resonance imaging (MRI) − ,, and to a lesser extent, magnetic particle imaging (MPI) . Additionally, EVs derived from tumor cells have been shown to improve delivery to parental tumor cells in vivo. − A recent study has used photoacoustic imaging to detect Prussian blue nanoparticles within an orthotopic brain tumor model in mice .…”