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Extending the In Vivo Residence Time of Macrophage Membrane-Coated Nanoparticles through Genetic Modification
Yaou Duan1, Jiarong Zhou1, Zhidong Zhou1
1Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, San Diego, CA, 92093, USA.
Small (Weinheim an Der Bergstrasse, Germany)
|August 27, 2023
Summary
Genetically engineering macrophages with PAS peptide chains prolongs nanoparticle residence time in vivo. This enhances their efficacy in treating inflammatory conditions like lung injury and endotoxemia.
Area of Science:
- Biomaterials Science
- Nanomedicine
- Genetic Engineering
Background:
- Cell membrane-coated nanoparticles are promising biomimetic nanomedicine.
- Macrophage membrane-coated nanoparticles offer versatile applications in drug delivery and biological neutralization.
- Enhancing in vivo residence time is crucial for improving nanoparticle performance.
Purpose of the Study:
- To enhance the in vivo residence times of macrophage membrane-coated nanoparticles using genetic engineering.
- To investigate the protective effects of proline-alanine-serine (PAS) peptide chains against opsonization and phagocytosis.
- To evaluate the impact of prolonged residence time on the therapeutic efficacy of these nanoparticles.
Main Methods:
- Genetic engineering of macrophages to express PAS peptide chains.
- Preparation of macrophage membrane-coated nanoparticles using wild-type and engineered membranes.
- Intravenous and intratracheal administration of nanoparticles in mouse models.
- Assessment of in vivo residence times and inhibition of inflammatory cytokines.
Main Results:
- Engineered nanoparticles exhibited significantly prolonged in vivo residence times compared to wild-type.
- PAS peptide chains effectively protected nanoparticles against opsonization and phagocytosis.
- Enhanced nanoparticle efficacy in inhibiting inflammatory cytokines in models of lung injury and endotoxemia was observed.
Conclusions:
- Genetic modification of macrophages with PAS peptides is an effective strategy to extend nanoparticle in vivo residence times.
- This approach improves the therapeutic performance of macrophage membrane-coated nanoparticles.
- The methodology can be applied to other cell membrane-coated nanoparticles for enhanced biomedical applications.
