An amphiphilic block copolymer with photocleavable nitrobenzyl moieties in the side chain of the hydrophobic block was successfully synthesized by a combination of atom transfer radical polymerization (ATRP) and the Cu(I)-catalyzed 1,3-dipolar cycloaddition of azide and alkynes. 2-(Trimethylsilyloxy)ethyl methacrylate (HEMATMS) was polymerized from a poly(ethylene oxide) (PEO) macroinitiator via ATRP, leading to a well-defined block copolymer of PE0113-b-PHEMATMS45 with low polydispersity index (PDI = 1.09). After the polymerization, trimethylsilyl (TMS) groups were deprotected and then functionalized in-situ with 3-azidopropionic chloride to yield PEO-b-[2-(1-azidobutyryloxy)ethyl methacrylate] (PEO-b-PAzHEMA). Alkyne-functionalized pyrene with a photocleavable 2-nitrobenzyl moiety was added to the PEO-b-PAzHEMA backbone via click chemistry to produce the desired block copolymer with high fidelity. The resulting block copolymer was self-assembled in water to yield spherical micelles with an average diameter of 60-nm. Upon UV irradiation, 2-nitrobenzyl moieties were selectively cleaved, leading to the release of a model drug, 1-pyrenebutyric acid. Coumarin 102, another model drug that was physically encapsulated in the core of micelles during micellization in water, was also released at the same time. The general strategy presented herein can potentially be utilized for the preparation of polymeric vehicles that are capable of delivering multiple therapeutics under controlled individual release kinetics. (C) 2014 Elsevier Ltd. All rights reserved.