Enzyme cleavable nanoparticles from peptide based triblock copolymers

• Published in: Nanoscale 2013-06, Vol.5 (11), p.4829-4839
• Main Authors: Fuchs, Adrian V, Kotman, Niklas, Andrieu, Julien, Mailänder, Volker, Weiss, Clemens K, Landfester, Katharina
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Block copolymers; Cleavage; Drug Carriers - chemistry; Enzymes; Humans; Hydrophobic and Hydrophilic Interactions; Male; Nanocomposites; Nanomaterials; Nanoparticles; Nanoparticles - chemistry; Nanostructure; Particle Size; Peptides; Peptides - chemical synthesis; Peptides - metabolism; Polystyrenes - chemistry; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Serine Endopeptidases - metabolism; Solid-Phase Synthesis Techniques; Trypsin - metabolism
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/c3nr00706e

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.