Tuning Particle Biodegradation through Polymer-Peptide Blend Composition

摘要

We report the preparation of polymerpeptide 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) (PEG(45)-b-P(DPA(55)-co-PgTEGMA(4))) and poly(l-histidine) (PHis). PEG(45)-b-P(DPA(55)-co-PgTEGMA(4)) 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 polymerpeptide 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 pi-pi stacking of the imidazole rings of PHis side chains at physiological pH (pH similar to 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.