Temperature and Photo Dual‐Stimuli Responsive Block Copolymer Self‐Assembly Micelles for Cellular Controlled Drug Release

To well adapt to the complicated physiological environments, it is necessary to engineer dual- and/or multi-stimuli responsive drug carriers for more effective drug release. For this, a novel temperature responsive lateral chain photosensitive block copolymer, poly[(N-isopropylacrylamide-co-N,N-dimethylacrylamide) -block-propyleneacylalkyl-4-azobenzoate] (P(NIPAM-co-DMAA)-b-PAzoHPA), is synthesized by atom transfer radical polymerization. The structure is characterized by 1 H nuclear magnetic resonance spectrometry and laser light scattering gel chromatography system. The self-assembly behavior, morphology, and sizes of micelles are investigated by fluorescence spectroscopy, transmission electron microscope, and laser particle analyzer. Dual responsiveness to light and temperature is explored by ultraviolet-visible absorption spectroscopy. The results show that the copolymer micelles take on apparent light and temperature dual responsiveness, and its lower critical solution temperature (LCST) is above 37 °C, and changes with the trans-/cis- isomerization of azobenzene structure under UV irradiation. The blank copolymers are nontoxic, whereas the paclitaxel (PTX)-loaded counterparts possessed comparable anticancer activities to free PTX, with entrapment efficiency of 83.7%. The PTX release from the PTX-loaded micelles can be mediated by changing temperature and/or light stimuli. The developed block copolymers can potentially be used for cancer therapy as drug controlled release carriers.