Involvement of autophagy in antitumor activity of folate-appended methyl-β-cyclodextrin.

Autophagy, the major lysosomal pathway for recycling intracellular components including organelles, is emerging as a key process regulating tumorigenesis and cancer therapy. Most recently, we newly synthesized folate-appended methyl-β-cyclodextrin (FA-M-β-CyD), and demonstrated the potential of FA-M-β-CyD as a new antitumor drug. In this study, we investigated whether anticancer activity of FA-M-β-CyD in folate receptor-α (FR-α)-positive tumor cells is involved in autophagy.

Potential use of the complex of doxorubicin with folate-conjugated methyl-β-cyclodextrin for tumor-selective cancer chemotherapy.

In a recent study, we attempted to confer a tumor-selective cytotoxic activity to methyl-β-cyclodextrin (M-β-CyD), we synthesized folate-conjugated M-β-CyD (FA-M-β-CyD), and demonstrated the potential of FA-M-β-CyD as a novel anticancer agent at a high dose. In the present study, to expand the application of FA-M-β-CyD for cancer chemotherapy, we evaluated the potential of FA-M-β-CyD as a tumor-targeting anticancer drug carrier at a low dose. FA-M-β-CyD formed an inclusion complex with doxorubicin (DOX) with a high-stability constant (3.

Design and evaluation of folate-appended α-, β-, and γ-cyclodextrins having a caproic acid as a tumor selective antitumor drug carrier in vitro and in vivo.

We reported that per-6-folic acid (FA)-appended β-cyclodextrin (β-CyD) possessing two caproic acids between FA and a β-CyD molecule as a spacer (Fol-c2-β-CyD) could be useful as a promising antitumor drug carrier. However, the effects of the cavity size and the spacer length on the carrier ability are not still known. In this study, we designed and evaluated the FA-appended three kinds of CyDs possessing a caproic acid as a spacer between FA and a CyD molecule (Fol-c1-CyDs) as a tumor targeting carrier for antitumor drugs.

Involvement of cholesterol depletion from lipid rafts in apoptosis induced by methyl-β-cyclodextrin.

Methyl-β-cyclodextrin (M-β-CyD), which is widely used as a lipid rafts disrupting agent, is known to induce cytotoxicity at high concentration. In the present study, we investigated the potential of M-β-CyD as an antitumor drug. M-β-CyD markedly caused apoptotic cell-death in KB cells, a human oral squamous carcinoma cell line, Ihara cells, a highly pigmented human melanoma cell line, and M213 cells, a human cholangiocarcinoma cell line, through cholesterol depletion in cell membranes.

Folate-appended β-cyclodextrin as a promising tumor targeting carrier for antitumor drugs in vitro and in vivo.

A large number of antitumor drug delivery carriers based on passive targeting and/or active targeting have been developed. However, encapsulation of antitumor drugs into these drug carriers is often complicated, and antitumor activities of these targeting systems are not satisfactory. In the present study, we first prepared heptakis-6-folic acid (FA)-appended β-cyclodextrin (β-CyD) possessing two caproic acids between FA and a β-CyD molecule as a spacer (Fol-c(2)-β-CyD) and evaluated the potential as a novel tumor targeting carrier for antitumor drugs through a complexation.

Potential use of folate-appended methyl-β-cyclodextrin as an anticancer agent.

To obtain a tumor cell-selectivity of methyl-β-cyclodextrin (M-β-CyD), we newly synthesized folate-appended M-β-CyD (FA-M-β-CyD), and evaluated the potential of FA-M-β-CyD as a novel anticancer agent in vitro and in vivo. Potent antitumor activity and cellular association of FA-M-β-CyD were higher than those of M-β-CyD in KB cells, folate receptor (FR)-positive cells. FA-M-β-CyD drastically inhibited the tumor growth after intratumoral or intravenous injection to FR-positive Colon-26 cells-bearing mice.