Near-infrared light sensitive polypeptide block copolymer micelles for drug delivery† Surjith Kumar, ab Jean-Francois Allard, c Denis Morris, c Yves L. Dory, * a Martin Lepage * b and Yue Zhao * a Received 5th December 2011, Accepted 2nd February 2012 DOI: 10.1039/c2jm16380b A new biocompatible block copolymer (BCP) composed of poly(ethylene oxide) (PEO) and poly(L-glutamic acid) bearing a number of 6-bromo-7-hydroxycoumarin-4-ylmethyl groups, PEO 114 -b-P(LGA 0.62 -co-COU 0.38 ) 34 , was prepared for near-infrared (NIR) light-induced drug delivery. We demonstrate that micelles of PEO 114 -b-P(LGA 0.62 -co-COU 0.38 ) 34 could be disrupted by 794 nm NIR light excitation via two-photon absorption. This was linked to the high two-photon absorption cross-section of the coumarin moiety. Disruption followed from the NIR light-induced removal of coumarin groups from the polypeptide block that shifted the hydrophilic–hydrophobic balance toward the destabilization of the micelles in aqueous solution. Using NIR light-triggered disruption of BCP micelles, we investigated the release of an antibacterial drug (Rifampicin) and an anticancer drug (Paclitaxel) loaded into the photosensitive BCP micelles. We found that the two drugs could be released effectively upon NIR light exposure of the micellar solution. To our knowledge, this is the first study of NIR light-triggered disruption of biocompatible polypeptide BCP micelles and its use for drug release. This is a step forward towards light-controllable drug delivery applications. Introduction In recent years, biocompatible micelles that are usually self- assembled from biocompatible amphiphilic polymers in water have emerged as one of the most promising nanocarrier systems for various hydrophobic drugs. 1 They offer several advantages, such as significantly enhancing drug water solubility, prolonging circulation time, targeting tumor tissues via the enhanced permeation and retention (EPR) effect, decreasing side effects, and improving drug bioavailability. 2 During the past two decades, there have been numerous reports on stimuli-sensitive block copolymer (BCP) micellar systems developed for controlled drug delivery. Changes in the physico-chemical properties of BCP micelles can be triggered by diverse stimuli such as ultrasound, 3 magnetic field, 4 electrical field, 5 enzymes, 6 temperature, 7 pH, 8 and light. 9 Among stimulus-responsive BCP micelles, those controlled by light are attractive, because the use of light enables remote activation of the release process and the drug release can be induced at a desired time at the light exposure site (spatial and temporal control). However, the majority of light-responsive photochromic moieties incorporated into the BCP structures absorb high-energy ultra-violet (UV) or visible light whose utility is limited in vivo and may be insufficient for many biological applications. To overcome this drawback, an increasing number of drug-delivery materials sensitive to near- infrared (NIR) light have been reported in recent years. 10 NIR light is more suitable for biomedical applications because it has a deeper penetration into live tissues and is less harmful to healthy cells than UV or visible light. The incorporation of light- absorbing nanoparticles that exhibit high absorption in the NIR range, along with thermo-sensitive polymers, has also been used for photothermal release. 11 For NIR light-sensitive BCP micelles, we have previously reported the syntheses and investigations of two amphiphilic BCPs of which the hydrophobic block is a polymethacrylate that contains either o-nitrobenzyl or coumarin moieties exhibiting two-photon absorption of NIR light. 12 In these cases, the NIR light-induced photolysis of the chromophores results in their removal from the poly- methacrylate and converts it to a hydrophilic poly(methacrylic acid), leading to the disruption of BCP micelles in aqueous solution. Although interesting, biocompatibility is an essential requirement for biomedical applications of NIR light-sensitive BCPs. This requirement significantly limits the possible types of polymers or copolymers to, for example, poly(ethylene oxide), poly(aspartic acid) or poly(glutamic acid). 13 To accomplish this a D epartement de chimie, Universit e de Sherbrooke, Sherbrooke, QC, Canada J1K 2R1. E-mail: yves.dory@usherbrooke.ca; yue.zhao@ usherbrooke.ca b D epartement de m edecine nucl eaire et radiobiologie and Centre d’imagerie mol eculaire de Sherbrooke, Universit e de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4. E-mail: martin.lepage@usherbrooke.ca c D epartement de physique, Universit e de Sherbrooke, Sherbrooke, QC, Canada J1K 2R1 † Electronic supplementary information (ESI) available: Experimental details, synthesis of monomers and polymers and characterization results using 1 H-NMR, SEC determination of CMC, and one-photon (UV) induced cleavage of micelles. See DOI: 10.1039/c2jm16380b 7252 | J. Mater. Chem., 2012, 22, 7252–7257 This journal is ª The Royal Society of Chemistry 2012 Dynamic Article Links C < Journal of Materials Chemistry Cite this: J. Mater. Chem., 2012, 22, 7252 www.rsc.org/materials PAPER Downloaded by Universite de Sherbrooke on 11 September 2012 Published on 05 March 2012 on http://pubs.rsc.org | doi:10.1039/C2JM16380B View Online / Journal Homepage / Table of Contents for this issue