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Smart insulin delivery platforms having the ability of mimicking pancreatic cells are highly expected for diabetes treatment. Herein, a smart glucose-sensitive insulin delivery platform on the basis of transcutaneous microneedles has been designed. The as-prepared microneedles are composed of glucose- and pH-responsive supramolecular polymer vesicles (PVs) as the drug storage and water soluble polymers as the matrix. The well-defined PVs are constructed from the host–guest inclusion complex between water-soluble pillar­[5]­arene (WP5) with pH-responsiveness and paraquat-ended poly­(phenylboronic acid) (PPBA-G) with glucose-sensitivity. The drug-loaded PVs, including insulin and glucose oxidase (GOx) can quickly respond to elevated glucose level, accompanied by the disassociation of PVs and fast release of encapsulated insulin. Moreover, the insulin release rate is further accelerated by GOx, which generates gluconic acid at high glucose levels, thus decreasing the local pH. Therefore, the host–guest interaction between WP5 and PPBA-G is destroyed and a total structure disassociation of PVs takes place, contributing to a fast release of encapsulated insulin. The in vivo insulin delivery to diabetic rats displays a quick response to hyperglycemic levels and then can fast regulate the blood glucose concentrations to normal levels, which demonstrates that the obtained smart insulin device has a highly potential application in the treatment of diabetes.

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Combination of photodynamic therapy and chemotherapeutic drugs is a promising strategy to achieve enhanced anticancer effect. In this study, a novel reactive oxygen species (ROS) synergistic pH/H2O2-responsive nanocomposite has been prepared from the self-assembly of poly­(l-lactic acid)-block-poly­(sodium 4-styrenesulfonate) in aqueous solution, followed by addition of ferric citrate (Cit-Fe­(III)) through electrostatic interaction and growing ZIF-8 among the surface of the particles. Upon H2O2 and visible light stimuli, efficient ROS such as hydroxyl radicals (•OH) and sulfate radicals (SO4 •–) can be generated through the catalyst of Cit-Fe­(III). Meanwhile, sulfonate-containing polymeric vesicles are disassembled through oxidization by ROS, and the encapsulated doxorubicin (DOX) will gradually diffuse into the ZIF-8 (one type of metal–organic framework, MOF) channels. The gatekeepers, ZIF-8, will collapse only under low pH condition, and a burst drug release is achieved. In the presence of H2O2 and pH stimuli upon visible light exposure, the prepared DOX-loaded nanocomposite exhibits good selectivity for both generating ROS and releasing drug in tumor cell instead of normal cell. The merits of nanocomposites such as good biocompatibility and especially the synergistic effect of chemo-photodynamic therapy make the material a highly promising candidate for drug delivery system in chemo-photodynamic therapy.

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