Lei Chen , Yang Song , Lian Deng , Jianpeng Liu , Jiabao Liu , Daobing Jiang , Xiaoshuang Dai , Ke Mei , Junda Liu , Neng Qiu
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引用次数: 0
Abstract
Podophyllotoxin (PPT) has excellent antitumor activity. However, poor water solubility and severe adverse effects hinder its extensive clinical applications. To effectively utilize PPT to fight against cancer, PPT was conjugated with adamantanamine (Ad) via glutathione (GSH) response disulfide bond and the resulting PPT-SS-AD was incorporated in β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) to generate high-affinity PPT-SS-AD/β-CD and PPT-SS-AD/HP-β-CD inclusion complexes. By conjugating with AD, the stability constants (Ks) of PPT-SS-AD/β-CDs were notably higher than that of PPT/β-CDs. In addition, the water solubility of PPT-SS-AD/β-CD and PPT-SS-AD/HP-β-CD increased 5.1-fold and 8.71-fold compared to free PPT, respectively. Both PPT-SS-AD/β-CD and PPT-SS-AD/HP-β-CD inclusion complexes exhibited accelerated release in the presence of DTT and at acidic condition. The inclusion complex with hydrophilic CD and hydrophobic PPT could self-assemble into nanosized particles with spherical shape. Cell uptake studies showed that uptake of PPT-SS-AD/β-CD NPs was 2.12-fold greater than that of PPT. Moreover, the in vitro studies showed that the cytotoxic effects of PPT-SS-AD/β-CD and PPT-SS-AD/HP-β-CD inclusion complexes were also enhanced compared to free PPT and the most significant cell growth inhibition was observed in Hela cells. Our study demonstrates the potential of utilizing adamantanamine modification to enhance the complexation of anticancer drugs with cyclodextrins and subsequently boosting the anticancer efficacy.
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