Tuning Particle Biodegradation through Polymer鈥揚eptide Blend Composition

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• 作者：Sylvia T. Gunawan ; Kristian Kempe ; Georgina K. Such ; Jiwei Cui ; Kang Liang ; Joseph J. Richardson ; Angus P. R. Johnston ; Frank Caruso
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：December 8, 2014
• 年：2014
• 卷：15
• 期：12
• 页码：4429-4438
• 全文大小：517K
• ISSN：1526-4602

文摘

We report the preparation of polymer鈥損eptide 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鈥損eptide 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 蟺鈥撓€ stacking of the imidazole rings of PHis side chains at physiological pH (pH 鈭?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.