title: Tuning particle biodegradation through polymer-peptide blend composition.
abstract: We report the preparation of polymer-peptide blend replica particles via the mesoporous silica (MS) templated assembly of poly(ethylene glycol)-block-poly(2-diisopropylaminoethyl methacrylate-co-2-(2-(2-(prop-2-ynyloxy)ethoxy)ethoxy)ethyl methacrylate) (PEG45-b-P(DPA55-co-PgTEGMA4)) and poly(l-histidine) (PHis). PEG45-b-P(DPA55-co-PgTEGMA4) was synthesized by atom transfer radical polymerization (ATRP), and was coinfiltrated with PHis into poly(methacrylic acid) (PMA)-coated MS particles assembled from different peptide-to-polymer ratios (1:1, 1:5, 1:10, or 1:15). Subsequent removal of the sacrificial templates and PMA resulted in monodisperse, colloidally stable, noncovalently cross-linked polymer-peptide blend replica particles that were stabilized by a combination of hydrophobic interactions between the PDPA and the PHis, hydrogen bonding between the PEG and PHis backbone, and π-π stacking of the imidazole rings of PHis side chains at physiological pH (pH ∼ 7.4). The synergistic charge-switchable properties of PDPA and PHis, and the enzymatic degradability of PHis, make these particles responsive to pH and enzymes. In vitro studies, in simulated endosomal conditions and inside cells, demonstrated that particle degradation kinetics could be engineered (from 2 to 8 h inside dendritic cells) based on simple adjustment of the peptide-to-polymer ratio used.
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Sylvia T
authors.initials: ST
authors.lastname: Gunawan
authors.forename: Kristian
authors.initials: K
authors.lastname: Kempe
authors.forename: Georgina K
authors.initials: GK
authors.lastname: Such
authors.forename: Jiwei
authors.initials: J
authors.lastname: Cui
authors.forename: Kang
authors.initials: K
authors.lastname: Liang
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Richardson
authors.forename: Angus P R
authors.initials: AP
authors.lastname: Johnston
authors.forename: Frank
authors.initials: F
authors.lastname: Caruso
mesh_terms: D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012822:Silicon Dioxide / Q000138:chemical synthesis
chemical_list: D008689:Methacrylates; D011108:Polymers; C008384:methacrylic acid; C033223:polyhistidine; D011092:Polyethylene Glycols; D006639:Histidine; D012822:Silicon Dioxide