Ligand-Specific Targeting of Microspheres to Phagocytes by Surface Modification with Poly(L-Lysine)-Grafted Poly(Ethylene Glycol) Conjugate
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Purpose. The purpose of this study was to demonstrate specific receptor-mediated targeting of phagocytes by functional surface coatings of microparticles, shielding from nonspecific phagocytosis and allowing ligand-specific interactions via molecular recognition.
Methods. Coatings of the comb polymer poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG) were investigated for potential to inhibit 1) nonspecific spreading of human blood-derived macrophages (MOs) and dendritic cells (DCs) on glass and 2) nonspecific phagocytosis of PLL-g-PEG-coated, carboxylated polystyrene (PS) or biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres. Coating was performed by adsorption of positively charged PLL-g-PEG on negatively charged microparticles or plasma-cleaned glass through electrostatic interaction. The feasibility of ligand-specific interactions was tested with a model ligand, RGD, conjugated to PEG chains of PLL-g-PEG to form PLL-g-PEG-RGD and compared with inactive ligand conjugate, PLL-g-PEG-RDG.
Results. Coatings with PLL-g-PEG largely impaired the adherence and spreading of MOs and DCs on glass. The repellent character of PLL-g-PEG coatings drastically reduced phagocytosis of coated PS and PLGA microparticles to 10% in presence of serum. With both MOs and DCs, we observed ligand-specific interactions with PLL-g-PEG-RGD coatings on glass and PS and PLGA microspheres. Ligand specificity was abolished when using inactive ligand conjugate PLL-g-PEG-RDG, whereas repellency of coating was maintained.
Conclusions. Coatings of PLL-g-PEG-ligand conjugates provide a novel technology for ligand specific targeting of microspheres to MOs and DCs while reducing nonspecific phagocytosis.
- Ligand-Specific Targeting of Microspheres to Phagocytes by Surface Modification with Poly(L-Lysine)-Grafted Poly(Ethylene Glycol) Conjugate
Volume 20, Issue 2 , pp 237-246
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers-Plenum Publishers
- Additional Links
- poly(D,L,-lactide-co-glycolide) (PLGA) microspheres
- surface modification
- poly(L-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG)
- Industry Sectors
- Author Affiliations
- 1. Laboratory of Applied Physics, Department of Physics and Measurement Technology, Linköping University, SE-581 83, Linköping, Sweden
- 2. Laboratory of Surface Science and Technology, Department of Materials, Swiss Federal Institute of Technology Zurich (ETH), Wagistrasse 2, 8952, Schlieren, Switzerland
- 3. Department of Applied Biosciences, Drug Formulation & Delivery Group, Swiss Federal Institute of Technology Zurich (ETH), Winterthurerstrasse 190, 8057, Zurich, Switzerland
- 4. Biomicrometrics Group, Department of Mechanical Engineering, Swiss Federal Institute of Technology Zurich (ETH), Wagistr. 4, 8952, Schlieren, Switzerland