Regulating Interactions Between Targeted Nanocarriers and Mononuclear Phagocyte System via an Esomeprazole-Based
Zakia Belhadj1, Bing He1, Jijun Fu2
1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China.
International Journal of Nanomedicine
|September 14, 2020
Summary
Esomeprazole (ESO) preconditioning reduces nanoparticle uptake by the mononuclear phagocyte system (MPS), enhancing nanomedicine circulation time and tumor targeting for improved cancer therapy.
Area of Science:
- Nanomedicine
- Cancer Therapy
- Immunology
Background:
- The mononuclear phagocyte system (MPS) hinders nanoparticle delivery to tumors.
- Improving nanoparticle circulation and tumor targeting is crucial for effective nanomedicine.
- Novel strategies are needed to overcome MPS-mediated clearance of nanocarriers.
Purpose of the Study:
- To develop a preconditioning strategy to enhance nanoparticle circulation and tumor targeting.
- To investigate the regulation of nanocarrier-MPS interactions using esomeprazole (ESO).
- To evaluate the efficacy of ESO-preconditioned nanomedicines in a tumor model.
Main Methods:
- In vitro evaluation of vacuolar H+-ATPase inhibitors on macrophage uptake of lipid vesicles.
- Selection and investigation of esomeprazole (ESO) as a preconditioning agent.
- In vivo studies using ESO pretreatment followed by injection of drug-loaded, targeted nanoparticles in tumor-bearing mice.
Main Results:
- ESO reduced macrophage uptake of nanoparticles by interfering with lysosomal trafficking in vitro.
- ESO pretreatment decreased nanoparticle accumulation in the liver and spleen in vivo.
- Enhanced tumor accumulation and improved therapeutic outcomes were observed with ESO-preconditioned nanomedicines.
Conclusions:
- Esomeprazole (ESO) effectively regulates nanoparticle-MPS interactions.
- ESO preconditioning offers a feasible strategy to enhance the tumor targeting of nanomedicines.
- This approach holds promise for improving cancer nanotherapy efficacy.
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