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Published on: December 5, 2018
M1 Macrophage-Derived Exosome-Mimetic Nanovesicles with an Enhanced Cancer Targeting Ability
Seungki Baek1, Miyeon Jeon1, Han Na Jung1
1Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.
Abstract:
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.
Insights
Surface modification of macrophage-derived nanovesicles (MNVs) with polyethylene glycol (PEG) significantly enhanced their circulation time and tumor targeting efficiency. This advancement improves the potential of nanovesicles as drug delivery vehicles for cancer immunotherapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Immunotherapy
Background:
- Extracellular vesicles (EVs) show promise as therapeutic drug delivery vehicles for diseases like cancer.
- Macrophage-derived exosome-mimetic nanovesicles (MNVs) can induce antitumor responses and improve immunotherapy efficacy.
- Limited in vivo tumor targeting of EVs due to rapid clearance by the reticuloendothelial system hinders their clinical application.
Purpose of the Study:
- To develop a surface modification strategy for MNVs to enhance their in vivo tumor targeting efficiency.
- To investigate the impact of polyethylene glycol (PEG) modification on MNV pharmacokinetics and biodistribution.
- To assess the potential of PEGylated MNVs for improved cancer drug delivery and immunotherapy.
Main Methods:
- Surface modification of MNVs using polyethylene glycol (PEG).
- Evaluation of blood circulation time of PEG-MNVs compared to bare MNVs in an animal tumor model.
- Quantification of protein content in MNVs relative to exosomes.
Main Results:
- PEG-MNVs exhibited a 7-fold increase in blood circulation time compared to bare MNVs.
- MNVs demonstrated a 25-fold higher protein content than exosomes.
- The study successfully enhanced the in vivo tumor targeting efficiency of MNVs through PEGylation.
Conclusions:
- Surface modification of MNVs with PEG is a viable strategy to overcome rapid clearance and improve in vivo tumor targeting.
- Enhanced nanovesicle circulation and targeting efficiency hold significant potential for advancing EV-based therapeutics.
- These nanovesicle preparation strategies may accelerate the clinical translation of extracellular vesicle-based therapies for various diseases.
