Reduction of the uptake by a macrophagic cell line of nanoparticles bearing heparin or dextran covalently bound to poly(methyl methacrylate)

Amphiphilic and fluorescent covalently labelled core-shell nanoparticles ba sed on poly (methyl methacrylate) (PMMA), were prepared by random copolymer isation of N-Vinyl carbazole (NVC) with MMA, initiated on polysaccharidic r adicals, yielding diblock copolymers of either dextran-P(MMA-NVC) (Nanodex* particles), or heparin-P(MMA-NVC) (Nanohep* particles). Nanoparticles made from random copolymers of P(MMA-NVC) (PMMA*) were used as controls. The in teractions between particles and a J774A1 murine macrophage-like cell line were quantified by direct measurement of the cell-associated fluorescence. The association with the cells occurred within 30 min. Nanodex* and Nanohep * showed considerably less association than the control PMMA* particles. So me of the particle uptake could be attributed to phagocytosis. but more tha n 50% of the cell-associated fluorescence persisted at low temperature or i n the presence of cytochalasin B, The results suggest that both the adsorpt ion and the internalisation processes can be inhibited by the presence of t he polysaccharide chains. In conclusion, these results confirm that nanopar ticles prepared with heparin or dextran chains on their surface, probably i n a brush-like configuration, show "stealth" properties in vitro as had pre viously been observed in vivo. If this biomimetic approach can also be appl ied to biodegradable polymers, these systems would provide at least an alte rnative to PEG-modified particles as long-circulating drug carriers systems or imaging agents.