This study examines the potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles functionalized with poly(zwitterion)-mannose brushes to target macrophages. Uptake studies with RAW 264.7 macrophages indicate that multiple mannose-binding sites in the grafted brushes facilitate interaction with the mannose receptor of the macrophages, resulting in approximately four times higher cellular uptake than nanoparticles with mannose monolayer coatings. To test the feasibility of the nanoparticles as long-circulating drug delivery vehicles, their multicomponent aggregation in blood plasma is analyzed using nanoparticle tracking analysis and compared to poly(ethylene glycol)-coated (PEGylated) particles, which are known to reduce aggregation. There is no significant difference in the aggregation behavior of the poly(zwitterion)-mannose grafted particles and the PEGylated control particles (≈760 particles in aggregates per 105 particles). In addition, the particle size in blood plasma is compared, which includes the protein corona, after 0, 8, and 15 h. Whereas there is no significant difference at longer time scales, the overall particle size of the poly(zwitterion)-mannose brush-grafted nanoparticles is ≈130 nm smaller than that of the PEGylated nanoparticles at shorter time scales, suggesting a smaller protein corona. All these results suggest that poly(lactic-co-glycolic acid nanoparticles functionalized with poly(zwitterion)-mannose brush grafts may be excellent candidates for targeted drug delivery to macrophages.
All Science Journal Classification (ASJC) codes
- Materials Science(all)
- Condensed Matter Physics
- macrophage targeting
- nanoparticle aggregation
- nanoparticle tracking analysis
- poly(lactide-co-glycolic acid) nanoparticles