Study on β-cyclodextrin-complexed nanogels with improved thermal response for anticancer drug delivery

For achievement of controllability in drug delivery, development of nanocarriers with thermal response is one of the most investigated stimulative strategies for oncological treatment. How to improve the thermosensitivity of the nanocarriers is an important factor for their successful drug delivery applications. In this study, a kind of complexed nanogels (PNACD) was developed by incorporating β-cyclodextrin (β-CD) into the nanogels of copolymers of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) during their polymerization via in situ crosslinking of N,N′-methylenebisacrylamide (MBA) as a crosslinker. The complexed PNACD nanogels displayed a significantly enhanced thermosensitivity near body temperature compared to the β-CD-free nanogels (PNA), which is probably associated with the rapid volumetric transformation during heating/cooling process due to the formation of complexed (decomplexed) structure between β-CD and PNIPAM element. The PNACD nanogels can be used for loading of an anticancer drug (doxorubicin, DOX) with an encapsulation efficiency of 54 ± 5%. The DOX-loaded nanogels displayed pH-/thermo-dual responsivenesses in drug release, which can be effectively internalized into KB cells (a human epithelial carcinoma cell line) to exert good anticancer bioactivity. This approach may enlighten design of novel nanocarriers for delivery of drugs beyond anticancer chemotherapeutic reagents.