Published: August 29, 2011 r2011 American Chemical Society 7385 dx.doi.org/10.1021/ma2010102 | Macromolecules 2011, 44, 7385–7393 ARTICLE pubs.acs.org/Macromolecules Surface-Grafted Stimuli-Responsive Block Copolymer Brushes for the Thermo-, Photo- and pH-Sensitive Release of Dye Molecules Surjith Kumar, †,‡ Yves L. Dory,* ,† Martin Lepage,* ,‡ and Yue Zhao* ,† † D epartement de chimie, Universit  e de Sherbrooke, Sherbrooke, Qu ebec J1K 2R1, Canada ‡ D epartement de m edecine nucl  eaire et de radiobiologie and Centre d’imagerie mol  eculaire de Sherbrooke, Universit  e de Sherbrooke, Sherbrooke, Qu ebec J1H 5N4, Canada b S Supporting Information 1. INTRODUCTION Polymer-based delivery systems, particularly with respect to targeted biomedical applications, such as controllable drug release, have attracted much attention in polymer chemistry, pharmaceutics, and biomaterials science. 1 As such, several platforms have been exploited for these purposes, including the fabrication of polymerprotein 2 and polymerdrug con- jugates, 3 micelles, 4 vesicles, 5 and dendrimers. 6 Although the controlled release from three-dimensional (3D) particles remains the predominant drug delivery method, interest has increased in surface-based delivery systems for the controlled release of therapeutic molecules. 7 At present, there is an increasing research effort focused on stimuli-responsive thin films and coatings that combine a wide range of fundamental scientific and commercial objectives. 8 These smart polymer films have been proposed for various applications, including drug delivery systems, 9 liquid crystal command layers, 10 antireflection coatings, 11 switchable friction, 12 and membrane permeation mechanisms. 13 While techniques such as spin-coating, self-assembled monolayers, and the Langmuir Blodgett method have been employed for the macromolecular assembly of ultrathin films, other coating methods have gained much popularity, most notably the layer-by-layer (LbL) and polymer brush techniques. The LbL self-assembly of macromo- lecules can be performed on a variety of substrate types and shapes with precisely controlled nanometer dimensions. 14 Using LbL-assembled films, several groups have demonstrated success- fully the delivery of highly charged biomacromolecules and the uptake and release of small model drug compounds. 15,16 Hydro- lytically degradable LbL films have been demonstrated for tunable drug release; 17 drug-conjugated polyelectrolyte prodrugs were added to the components of the films, and cell viability was assayed. 18 Recently, we and other groups have reported the fabrication of LbL films of amphiphilic block copolymer micelles where hydrophobic compounds could be loaded into the micelle core. 19 However, the LbL techniques are generally limited to the use of charge-opposing polyelectrolytes, which are not generally thought to be good candidates for lipophilic drug-loading. Thus, development of thin film-based delivery systems for hydrophobic compounds is of interest. Received: May 3, 2011 Revised: August 17, 2011 ABSTRACT: We present a general approach for using surface-grafted stimuli-responsive diblock copolymer brushes as stimuli-sensitive and controllable release systems. Surface-initiated ATRP was used to grow sequentially a first block serving as an inner reservoir for loading and a second block that acts as a stimuli-responsive outer layer controlling the closure or opening of the brush in water. We show that the release kinetics of loaded model dyes (hydrophobic or hydrophilic) could be controlled by the second block switchable between the collapsed and extended brush chain states in response to temperature or pH change or exposure to light. On the one hand, diblock copolymer brushes of polystyrene-b-poly(N-isopropylacrylamide) (PS-b-PNIPAM) and poly(N,N 0 -dimethylacrylamide)-b-poly(N-isopropylacrylamide) (PDMA-b-PNIPAM) were synthesized to demonstrate the thermosensitive release of dyes based on the LCST-determined solubility switching between swollen and collapsed PNIPAM chains. On the other hand, a diblock copolymer brush of polystyrene-b-poly(4,5-dimethoxy-2-nitrobenzyl methacrylate) (PS-b- PNBA) was designed to investigate the possibility of tuning the dye release kinetics with light. The photocontrol was achieved by controlling the photocleavage degree of photolabile o-nitrobenzyl groups, which determines the number of hydrophilic methacrylic acid (MA) groups in the outer layer. Moreover, complete photocleavage of o-nitrobenzyl groups converted the photosensitive PS-b- PNBA brush into a pH-sensitive PS-b-PMA brush with which pH-dependent dye release was observed due to the water solubility switching of PMA chains with protonated or ionized carboxylic acid groups. The interest, the versatility, and the generality of the approach were demonstrated in this study with three different stimuli, namely, temperature, pH, and light.