Enzyme cleavable nanoparticles from peptide based triblock copolymers

作者: Adrian V. Fuchs , Niklas Kotman , Julien Andrieu , Volker Mailänder , Clemens K. Weiss

DOI: 10.1039/C3NR00706E

关键词:

摘要: 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 have potential application as a drug delivery system. Two different peptide sequences, one cleaved by trypsin (GFF), other hepsin (RQLRVVGG), overexpressed in early stages prostate cancer, used central part triblock. For fluorophore–quencher pair introduced around cleavage sequence. The solid phase conduced such that two identical sequences synthesized from branching point. Eventually, carboxy-terminated polystyrene into synthesizer coupled amino-termini branched Upon cleavage, fragment released copolymer, which has use applications. Conducting whole on avoids solubility issues post-synthetic purification steps. Due hydrophobic PS-chains, copolymer can easily be formulated form using nanoprecipitation process. Incubation with respective enzymes leads significant increase fluorescence incorporated fluorophore, thereby indicating sequence decomposition particles.

参考文章(51)
Roderic P. Quirk, Wei-Chih Chen, Functionalization of polymeric organolithium compounds. Carbonation Macromolecular Chemistry and Physics. ,vol. 183, pp. 2071- 2076 ,(1982) , 10.1002/MACP.1982.021830905
Ralph Weissleder, Ching-Hsuan Tung, Umar Mahmood, Sebastian Bredow, In vivo imaging of proteolytic enzyme activity using a novel molecular reporter. Cancer Research. ,vol. 60, pp. 4953- 4958 ,(2000)
Olivier J. Cayre, Nelly Chagneux, Simon Biggs, Stimulus responsive core-shell nanoparticles: synthesis and applications of polymer based aqueous systems Soft Matter. ,vol. 7, pp. 2211- 2234 ,(2011) , 10.1039/C0SM01072C
P. D. Thornton, R. J. Mart, R. V. Ulijn, Enzyme-responsive polymer hydrogel particles for controlled release Advanced Materials. ,vol. 19, pp. 1252- 1256 ,(2007) , 10.1002/ADMA.200601784
Matthias Maier, Niklas Kotman, Cornelius Friedrichs, Julien Andrieu, Manfred Wagner, Robert Graf, Wolfgang S. L. Strauss, Volker Mailänder, Clemens K. Weiss, Katharina Landfester, Highly Site Specific, Protease Cleavable, Hydrophobic Peptide–Polymer Nanoparticles Macromolecules. ,vol. 44, pp. 6258- 6267 ,(2011) , 10.1021/MA201149B
Kyle N. Plunkett, Kimberly L. Berkowski, Jeffrey S. Moore, Chymotrypsin responsive hydrogel: application of a disulfide exchange protocol for the preparation of methacrylamide containing peptides. Biomacromolecules. ,vol. 6, pp. 632- 637 ,(2005) , 10.1021/BM049349V
Yang Li, Ying Tan, Zhigang Ning, Sumiao Sun, Yuan Gao, Pixin Wang, Design and fabrication of fluorescein-labeled starch-based nanospheres Carbohydrate Polymers. ,vol. 86, pp. 291- 295 ,(2011) , 10.1016/J.CARBPOL.2011.04.049
Soyeon Kim, Eugene H. Chung, Michele Gilbert, Kevin E. Healy, Synthetic MMP‐13 degradable ECMs based on poly(N‐isopropylacrylamide‐co‐acrylic acid) semi‐interpenetrating polymer networks. I. Degradation and cell migration Journal of Biomedical Materials Research Part A. ,vol. 75, pp. 73- 88 ,(2005) , 10.1002/JBM.A.30375
Julien Andrieu, Niklas Kotman, Matthias Maier, Volker Mailänder, Wolfgang S. L. Strauss, Clemens K. Weiss, Katharina Landfester, Live Monitoring of Cargo Release From Peptide-Based Hybrid Nanocapsules Induced by Enzyme Cleavage Macromolecular Rapid Communications. ,vol. 33, pp. 248- 253 ,(2012) , 10.1002/MARC.201100729