Extracellular vesicles (EVs) have been found to be effective therapeutic drug delivery vehicles in a wide range of human diseases, including cancer and neurodegenerative diseases. Proinflammatory (M1) macrophages can modulate the suppressive immune environment of tumor tissues to be more inflammatory and have been considered as candidates for cancer immunotherapy. Furthermore, macrophage-derived exosome-mimetic nanovesicles (MNVs) could effectively induce antitumor response and enhance the efficacy of immune checkpoint inhibitors in a recent paper. However, multiple studies indicate that EVs were rapidly cleared by the reticuloendothelial system, and therefore, their tumor targeting efficiencies were limited. Herein, we developed a simple surface modification method of MNVs using polyethylene glycol (PEG) to enhance the in vivo tumor targeting efficiency. PEG-MNVs had 7-fold higher blood circulation than bare MNVs in the animal tumor model. Also, MNVs had a 25-fold higher protein amount than exosomes. Overall, the nanovesicle preparation strategies presented in this study may expedite the clinical translation of EV-based therapeutics in various diseases.
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