Session 4: Cell-Material Interaction

For nanoparticles that are used as intravascular drug delivery systems, aggregation resulting in carrier sizes >250 nm is a serious issue as those systems are removed from the blood stream by Kupffer cells.[4]Herein, we describe the synthesis of polylactide particles decorated by a polyglutamic acid corona by non-aqueous emulsion polymerization.While in many other approaches polypeptides are either after particle formation adsorbed or grafted herein we us a specially designed emulsifier to form a polypeptide shell.A light sensitive PEG-block-poly((1-pyrenyl methyl) glutamate) (PEG-b-PGlu(Pyr)) copolymer is synthesized and used as emulsifier in a nonaqueous emulsion polymerization of lactide which is required due to the moisture sensitivity of the polymerization catalysts.Poly(L-lactide) (PLLA) nanoparticles were synthesized via ring-opening polymerization of L-lactide with a moisture-sensitive catalyst in a non-aqueous emulsion consisting of acetonitrile, cyclohexane, and the PEG-b-PGlu(Pyr) copolymer as emulsifier.Upon UV irradiation, hydrophobic pyrenyl methylene units are cleaved from the block copolymer, resulting in a polarity reversal of the particle surface from hydrophobic to hydrophilic.The product particles have a fully hydrophilic and biocompatible PEG-b-PGlu shell and can be dispersed in water without aggregation.Furthermore, introducing MMP-3 cleavable peptide sequences in the nanoparticles allows for a full degradation of the particles when they are getting close to tumor cells.This offers the opportunity to selectively release drugs which have already been incorporated before during in the particle formation.The particles consist exclusively of non-toxic biodegradable polymes (polylactide and polypeptide making them suitable candidates for medical applications in particular for cancer therapy.