In Vitro Cytotoxicity, Chemotactic Effect, and Cellular Uptake of Branched Polypeptides with Poly[l-Lys] Backbone by J774 Murine Macrophage Cell Line

Abstract

Branched polypeptides with polylysine backbone are promising candidates for selective delivery of drugs, epitopes. or reporter molecules. We reported earlier that polylysine-based polypeptides with polyanionic character were internalized by murine bone marrow derived macrophages via class A scavenger receptor. In the present studies, our investigations were extended to seven polypeptides with different amino acid composition and charge properties. We report on our findings on the concentration-dependent influence of these compounds on survival and chemotaxis of the murine macrophage-like cell line J774 and internalization properties of the polypeptides by J774 cells. Our observations indicate that the polypeptides regardless of their charge properties were essentially nontoxic and did not alter significantly the chemotaxis of J774 cells; therefore, the polypeptides suit the requirements for nontoxic and "neutral" carrier molecules. We also demonstrated that the polypeptides were internalized efficiently by J774 cells, depending on their chemical structure and charge properties. Using the scavenger receptor-ligand fucoidan as inhibitor, we established that the scavenger receptor played a role-in accordance with findings on murine bone marrow derived macrophages in the internalization only of the polyanionic polypeptides.