Selective binding and controlled release of anticancer drugs by polyanionic cyclodextrins

The binding stoichiometry, binding constants, and inclusion mode of some water-soluble negatively charged cyclodextrin derivatives, i.e. heptakis-[6-deoxy-6-(3-sulfanylpropanoic acid)]-beta-cyclodextrin (H1), heptakis-[6-deoxy-6-(2-sulfanylacetic acid)]-beta-cyclodextrin(H2), mono-[6-deoxy-6-(3-sulfanylpropanoic acid)]-beta-cyclodextrin (H3) and mono-[6-deoxy-6-(2-sulfanylacetic acid)]-beta-cyclodextrin (H4), with three anticancer drugs, i.e. irinotecan hydrochloride; topotecan hydrochloride; doxorubicin hydrochloride, were investigated by means of H-1 NMR, UV-Vis spectroscopy, mass spectra and 2D NMR. Polyanionic cyclodextrins H1-H2 showed the significantly high binding abilities of up to 2.6 x 10(4)-2.0 x 10(5) M-1 towards the selected anticancer drugs, which were nearly 50-1000 times higher than the corresponding Ks values of native beta-cyclodextrin. In addition, these polyanionic cyclodextrins also showed the pH-controlled release behaviors. That is, the anticancer drugs could be efficiently encapsulated in the cyclodextrin cavity at a pH value similar to that of serum but sufficiently released at an endosomal pH value of a cancer cell, which would make these cyclodextrin derivatives the potential carriers for anticancer drugs. (C) 2018 Elsevier Ltd. All rights reserved.