The use of diselenide core cross-linked polymeric micelles assisted with indocyanine green (ICG) as a near-infrared (NIR)-responsive drug delivery system was known to be promising in terms of well-controlled release as well as biocompatibility. However, we must note that the effect of NIR exposure is not simply promoting cleavage of Se–Se bonds. In this work, we report a systematic investigation to the effect of NIR light exposure on the polymeric micelles of poly(ethylene glycol)-block-poly(styrene-alt-maleic anhydride) loaded with ICG. Diselenide core-cross-linked micelles and non-cross-linked micelles were prepared for the investigation. The results showed that the reactive oxygen species (ROS) produced from ICG not only reacted with diselenide bonds but also attacked poly(ethylene glycol) chains, resulting in the polymer degradation. The polymer degradation appeared to be continuous even for 36 h after NIR exposure was stopped, as evidenced in DLS, GPC, and TEM measurements. This study provides insight into essential parameters which should be considered in designing ROS-responsive drug delivery systems based on polymeric micelles.
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