[Development of Cyclodextrin-based Cancer Treatment]

Area of Science:

• Biomedical Engineering
• Drug Delivery
• Oncology

Background:

• Folic acid (FA) targets tumors via folate receptor-α (FR-α) overexpression.
• Methyl-β-cyclodextrin (M-β-CyD) induces cell death but lacks tumor selectivity.
• Developing targeted drug delivery systems is crucial for cancer therapy.

Purpose of the Study:

• To synthesize and evaluate folate-appended M-β-CyD (FA-M-β-CyD) as a novel tumor-selective anticancer agent.
• To investigate the mechanism of FA-M-β-CyD's antitumor activity.
• To assess the in vivo efficacy of FA-M-β-CyD in preclinical cancer models.

Main Methods:

• Synthesis of FA-M-β-CyD conjugate.
• In vitro evaluation of cytotoxicity against FR-α-positive and negative cancer cells.
• Investigation of autophagy induction by FA-M-β-CyD.
• In vivo antitumor efficacy studies in mouse models.

Main Results:

• FA-M-β-CyD demonstrated potent antitumor activity against FR-α-positive cells (KB, Ihara, M213) but not FR-α-negative cells (A549).
• FA-M-β-CyD induced autophagy in KB cells, and its activity was inhibited by autophagy inhibitors.
• Intravenous administration of FA-M-β-CyD significantly inhibited tumor growth and improved survival rates in mice.

Conclusions:

• FA-M-β-CyD is a promising tumor-selective anticancer agent mediated by FR-α uptake.
• FA-M-β-CyD's mechanism involves autophagy induction.
• This study provides a foundation for developing novel cyclodextrin-based antitumor drugs and drug carriers.