{'fraction_non_alphanumeric': 0.06361520558572537, 'fraction_numerical': 0.012412723041117145, 'mean_word_length': 4.657894736842105, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Supramolecular Complex of Methyl-β-cyclodextrin with Adamantane-Grafted Hyaluronic Acid as a Novel Antitumor Agent.

Methyl-β-cyclodextrin (M-β-CyD) exhibits cytotoxic activity, and has the potentials as an antitumor agent. However, a tumor-selectivity of M-β-CyD is low, leading to low antitumor activity and the adverse effects. Meanwhile, hyaluronic acid (HA) is known as a promising tumor targeting ligand, because various cancer cells overexpress CD44, a HA-binding glycoprotein. In the present study, to develop a tumor-selective delivery system for M-β-CyD, we designed a supramolecular complex of M-β-CyD with adamantane-grafted HA (Ad-HA/M-β-CyD) and evaluated it as a tumor-selective antitumor agent. M-β-CyD formed a stable complex with Ad-HA (Kc>104 M-1). In addition, Ad-HA/M-β-CyD formed slightly a negative-charged nanoparticle with ca. 140 nm of a particle size, indicating the favorable physicochemical properties for antitumor agents. Ad-HA/M-β-CyD showed the superior cytotoxic activity via CD44-mediated endosomal pathways in HCT116 cells (CD44(+)), a human colon cancer cell line. In addition, cytotoxic activity of Ad-HA/M-β-CyD was induced by apoptosis. These results suggest that Ad-HA/M-β-CyD has the potentials as a tumor-selective supramolecular antitumor agent.