pH-Induced Vesicle-to-Micelle Transition in Amphiphilic Diblock Copolymer: Investigation by Energy Transfer between in Situ Formed Polymer Embedded Gold Nanoparticles and Fluorescent Dye Chiranjit Maiti, Rakesh Banerjee, Saikat Maiti, and Dibakar Dhara* Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India * S Supporting Information ABSTRACT: The ability to regulate the formation of nanostructures through self-assembly of amphiphilic block copolymers is of immense significance in the field of biology and medicine. In this work, a new block copolymer synthesized by using reversible addition-fragmentation chain transfer (RAFT) polymerization technique from poly(ethylene glycol) monomethyl ether acrylate (PEGMA) and Boc-L- tryptophan acryloyloxyethyl ester (Boc-L-trp-HEA) was found to spontaneously form pH-responsive water-soluble nano- structures after removal of the Boc group. While polymer vesicles or polymerosomes were formed at physiological pH, the micelles were formed at acidic pH (< 5.2), and this facilitated a pH-induced reversible vesicle-to-micelle transition. Formation of these nanostructures was confirmed by different characterization techniques, viz. transmission electron microscopy, dynamic light scattering, and steady-state fluorescence measurements. Further, these vesicles were successfully utilized to reduce HAuCl 4 and stabilize the resulting gold nanoparticles (AuNPs). These AuNPs, confined within the hydrophobic shell of the vesicles, could participate in energy transfer process with fluorescent dye molecules encapsulated in the core of the vesicles, thus forming a nanometal surface energy transfer (NSET) pair. Subsequently, following the efficiency of energy transfer between this pair, it was possible to monitor the process of transition from vesicles to micelles. Thus, in this work, we have successfully demonstrated that NSET can be used to follow the transition between nanostructures formed by amphiphilic block copolymers. ■ INTRODUCTION Nanostructures from block copolymers, particularly from amphiphilic block copolymers, have aroused great interest among researchers because of their potential use in cosmetics, catalysis, electronics, and drug delivery. 1-4 The self-assembly of amphiphilic block copolymer molecules that leads to the formation of the nanostructures in aqueous systems depends on the hydrophobic-hydrophilic balance of the block copolymers. Stimuli responsive amphiphilic block polymers are even more attractive owing to their ability to generate versatile nano- structured assemblies such as micelles 5,6 and vesicles 2,7,8 and hence have the potential to be effective as stimuli sensitive delivery vehicles for therapeutics. 1,2,8,9 A great deal of effort has been focused on the synthesis of stimuli responsive block copolymers that are capable of undergoing conformational changes or phase transitions in solution with change in external stimuli like pH, temperature, and ionic strength. 7,10,11 Most of the methods for preparation of vesicles from amphiphilic molecules typically involve the use of an organic solvent such as tetrahydrofuran, N,N-dimethylformamide (DMF), or dioxane. 12-14 This method, however, is not preferred because of the toxicity associated with the organic solvents. Elaborate purification methods like dialysis are generally required to remove the organic solvent, making the process cost-ineffective. Furthermore, dialysis rate and solvent dependence on self-assembly are difficult to control. In this regard, water-soluble block copolymers that spontaneously form vesicles are highly desirable. Additionally, polymer vesicles or polymersomes made of amphiphilic copolymers have an aqueous core separated from the outside by a hydrophobic membrane with both external and internal surfaces formed by hydrophilic polymer. 12,15-17 Thus, vesicles can encapsulate both hydrophobic and hydrophilic molecules. If a vesicle can be transitioned to micelle in situ by a stimulus, then the hydrophilic molecules can be selectively released from the vesicles’ hydrophilic core. 18-20 In the present work, we have synthesized a new diblock copolymer by using the reversible addition-fragmentation chain transfer (RAFT) polymerization technique from highly biocompatible monomers poly(ethylene glycol) monomethyl ether acrylate (PEGMA) and Boc-L- tryptophan acryloyloxyethyl ester (Boc-L-trp-HEA). The Boc group deprotected block copolymer spontaneously forms vesicles in aqueous solution at physiological pH, which can be reversibly transitioned to micelles by changing the pH of the Received: June 30, 2014 Revised: December 12, 2014 Published: December 15, 2014 Article pubs.acs.org/Langmuir © 2014 American Chemical Society 32 DOI: 10.1021/la504165e Langmuir 2015, 31, 32-41