pH/redox/UV irradiation multi-stimuli responsive nanogels from star copolymer micelles and Fe3+ complexation for on-demand anticancer drug delivery

Multi-stimuli responsive nanogels, as promising drug carriers for on-demand drug delivery, are expected to provide promising prospects for tumour treatment. Herein, new pH/redox/UV irradiation multi-stimuli responsive nanogels, based on polymer micelles self-assembled by six-arm star copolymer of 6AS-PCL-PAAPPEGMA, were prepared by the complexation of ferric ions (Fe3+) and the carboxyl groups in the polymer micelles. The spherical structure of the polymer micelles, with particle size around 80-110 nm and zeta potential of - 30.19 mV, was more conducive to crosslinking with Fe3+ and quickly formed nanogels with the bigger size around 150-200 nm. The DOX-loaded nanogels were obtained by introducing the anticancer drug doxorubicin (DOX) in the nanogels preparation process with a drug loading content (DLC) of 12.04%. Under the exposure to UV, an introduction of a reducing agent (GSH) and a pH response from the PAA block, the nanogels underwent decrosslinking, followed by rapid DOX release (82.1% at 116 h). Moreover, the DOX-loaded nanogels not only could be taken up quickly by HepG2 cells but also inhibited the proliferation of the cells. Hence, these results demonstrated the high potential of the prepared 6AS-PCL-PAA-PPEGMA nanogels for on-demand anticancer drug delivery.