Stimulative nanogels with enhanced thermosensitivity for therapeutic delivery via β-cyclodextrin-induced formation of inclusion complexes

To explore the potential biomedical application of thermoresponsive nanosystems, it is important to enhance their thermosensitivity to improve the controllability in delivery of therapeutic agents. The present work develops multifunctional nanogels with enhanced thermosensitivity through copolymerization of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) in the presence of β-cyclodextrin (β-CD), using N,N′-bis(acryloyl)cystamine (BAC) as a biodegradable crosslinker. The resulting nanogels display significantly improved sensitivity in deswelling (swelling) behavior upon temperature increase (decrease) around body temperature. The nanogels can effectively encapsulate doxorubicin (DOX), which can be released in an accelerated way under microenvironments that mimic intracellular reductive conditions and acidic tumor tissues. Release can also be remotely manipulated by increasing temperature. In vitro study indicates that the nanogels are quickly taken up by KB cells (a human epithelial carcinoma cell line), exerting improved anticancer cytotoxicity, showing their potential for delivery of therapeutic agents beyond anticancer drugs.