title: Enzyme cleavable nanoparticles from peptide based triblock copolymers.
abstract: A solid-phase synthesis based approach towards protease cleavable polystyrene-peptide-polystyrene triblock copolymers and their formulation to nanoparticulate systems is presented. These nanoparticles are suitable for the optical detection of an enzyme and have the potential for application as a drug delivery system. Two different peptide sequences, one cleaved by trypsin (GFF), the other by hepsin (RQLRVVGG), a protease overexpressed in early stages of prostate cancer, are used as the central part of the triblock. For optical detection a fluorophore-quencher pair is introduced around the cleavage sequence. The solid phase synthesis is conduced such that two identical sequences are synthesized from one branching point. Eventually, carboxy-terminated polystyrene is introduced into the peptide synthesizer and coupled to the amino-termini of the branched sequence. Upon cleavage, a fragment is released from the triblock copolymer, which has the potential for use in drug delivery applications. Conducting the whole synthesis on a solid phase in the peptide synthesizer avoids solubility issues and post-synthetic purification steps. Due to the hydrophobic PS-chains, the copolymer can easily be formulated to form nanoparticles using a nanoprecipitation process. Incubation of the nanoparticles with the respective enzymes leads to a significant increase of the fluorescence from the incorporated fluorophore, thereby indicating cleavage of the peptide sequence and decomposition of the particles.
authors.affiliation: Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Adrian V
authors.initials: AV
authors.lastname: Fuchs
authors.forename: Niklas
authors.initials: N
authors.lastname: Kotman
authors.forename: Julien
authors.initials: J
authors.lastname: Andrieu
authors.forename: Volker
authors.initials: V
authors.lastname: Mailänder
authors.forename: Clemens K
authors.initials: CK
authors.lastname: Weiss
authors.forename: Katharina
authors.initials: K
authors.lastname: Landfester
mesh_terms: D000595:Amino Acid Sequence; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D011137:Polystyrenes / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D012697:Serine Endopeptidases / Q000378:metabolism*; D060327:Solid-Phase Synthesis Techniques; D014357:Trypsin / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D010455:Peptides; D011137:Polystyrenes; D012697:Serine Endopeptidases; C055645:hepsin; D014357:Trypsin