6136 DOI: 10.1021/la100644s Langmuir 2010, 26(9), 6136–6139 Published on Web 04/01/2010 pubs.acs.org/Langmuir © 2010 American Chemical Society Plasmonic Nanorods Provide Reversible Control over Nanostructure of Self-Assembled Drug Delivery Materials Wye-Khay Fong, † Tracey L. Hanley, ‡ Benjamin Thierry, § Nigel Kirby, ) and Ben J. Boyd* ,† † Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia, ‡ Bragg Institute, Australian Nuclear Science and Technology Organisation, Menai, NSW 2234, Australia, § Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA 5095, Australia, and ) SAXS/WAXS beamline, Australian Synchrotron, Clayton, Victoria, Australia Received February 11, 2010. Revised Manuscript Received March 11, 2010 The nanostructure of mesophase liquid crystals prepared from amphiphilic lipids controls the rate of release of incorporated agents from the material, such as drug molecules, and reversible transition between different nanos- tructures essentially provides an “on-off” switch for release (Fong, W.-K.; Hanley, T.; Boyd, B. J. J. Controlled Release 2009, 135, 218-226). In this study, the incorporation of plasmonic hydrophobized gold nanorods (GNRs) permits reversible manipulation of nanostructure on-demand, by irradiation of the matrix using a near-infrared laser. Synchrotron small-angle X-ray scattering was used to probe the kinetics of the response of nanostructure to laser irradiation, and the specificity of the approach is shown by the lack of response in the absence of nanorods, or for GNR whose dimensions are not matched to the specific wavelength of the incident light. Light sensitive systems are of increasing interest to researchers in applications such as drug delivery due to the noninvasive and remote nature by which the stimulus can be applied. Numerous light sensitive self-assembled systems including polymeric mi- celles, gels, liposomes, and nanocomposites have been reported and reviewed. 2,3 However, their translation into products, parti- cularly in the drug delivery field, has thus far been limited in part by the need to incorporate dyes or other light sensitive compo- nents of unknown toxicity. Lyotropic liquid crystals are receiving increasing interest as stimuli responsive materials for drug delivery. The self-assembled nanos- tructures are often thermodynamically stable in excess water 4 and comprise discrete lipidic domains and aqueous channels which allow the incorporation of molecules of varying physicochemical proper- ties. 5-11 The rate of release of a drug is dictated by its size relative to that of the aqueous channels which in turn is dictated by the overall geometry of the liquid crystalline structure, and the specific local packing of the amphiphilic lipids comprising the matrix. The inverse bicontinuous cubic and hexagonal phases (denoted v 2 and H 2 , respectively), and inverse micellar phase (L 2 ), illus- trated in Figure 1, are of particular interest in drug delivery. Transitions between these structures can be induced through changes in lipid packing. Temperature has been used as a stimulus to change liquid crystalline structure between the v 2 and H 2 structures in vitro and in vivo, demonstrating the potential of these systems as stimulus responsive delivery systems. Reversible switching between the v 2 and H 2 phase structures formed by the amphiphilic lipid 3,7,11,15-tetramethyl hexadecyl-1,2,3-triol (phytantriol, see Figure 1) using temperature provided a means to manipulate drug release. 1 However, the matrix required the inclusion of a modifier (vitamin E acetate) to reduce the transition temperature to close to physiological temperature for in vivo application, thereby enabling control over structure by applica- tion of, for example, a heat pack to the skin surface after subcutaneous administration. This is a major limitation, as there is no specificity in heat source; hence, exposure to extremes of temperature may unintentionally induce drug release. Conse- quently, an alternative means to induce the phase transition was necessary that did not require direct heating, and did not require a reduction in the temperature at which the transition occurs, ideally occurring at the inherent transition temperature without additive (approximately 55 °C for phytantriol), removing the potential for accidental activation. The incorporation of azo- containing surfactants was considered, but this has only been reported for modifying the ordering in lamellar phases rather than transitions between other liquid crystalline structures. 12,13 Toward the design of an advanced drug delivery system based on light-triggered phase transition of liquid crystalline phases, we report here the design of novel liquid crystalline matrix-gold nano- rod hybrid materials. Hydrophobized gold nanorods (GNRs) have been incorporated within the liquid crystalline matrix to provide remote heating, and trigger the phase transitions on irradiation at close to their resonant wavelength. The surface of plasmonic metal nanoparticles delivers heat into surrounding material on *To whom correspondence should be addressed. Telephone: þ61 3 99039112. Fax: þ61 3 99039583. E-mail: ben.boyd@pharm.monash.edu.au. (1) Fong, W.-K.; Hanley, T.; Boyd, B. J. J. Controlled Release 2009, 135, 218–226. (2) Alvarez-Lorenzo, C.; Bromberg, L.; Concheiro, A. Photochem. Photobiol. 2009, 85, 848–860. (3) Christie, J. G.; Kompella, U. B. Drug Discovery Today 2008, 13, 124–134. (4) Kaasgaard, T.; Drummond, C. J. Phys. Chem. Chem. Phys. 2006, 8, 4957–4975. (5) Drummond, C. J.; Fong, C. Curr. Opin. Colloid Interface Sci. 1999, 4, 449–456. (6) Lee, K. W. Y.; Nguyen, T.-H.; Hanley, T.; Boyd, B. J. Int. J. Pharm. 2009, 365, 190–199. (7) Shah, J. C.; Sadhale, Y.; Chilukuri, D. M. Adv. Drug Delivery Rev. 2001, 47, 229–250. (8) Amar-Yuli, I.; Libster, D.; Aserin, A.; Garti, N. Curr. Opin. Colloid Interface Sci. 2009, 14, 21–32. (9) Boyd, B. J.; Khoo, S.-M.; Whittaker, D. V.; Davey, G.; Porter, C. J. H. Int. J. Pharm. 2007, 340, 52–60. (10) Boyd, B. J.; Whittaker, D. V.; Khoo, S.-M.; Davey, G. Int. J. Pharm. 2006, 318, 154–162. (11) Cervin, C.; Vandoolaeghe, P.; Nistor, C.; Tiberg, F.; Johnsson, M. Eur. J. Pharm. Sci. 2009, 36, 377–385. (12) Eastoe, J.; Vesperinas, A. Soft Matter 2005, 1, 338–347. (13) Zou, A.; Eastoe, J.; Mutch, K.; Wyatt, P.; Scherf, G.; Glatter, O.; Grillo, I. J. Colloid Interface Sci. 2008, 322, 611–616.