Nanoparticles of folic acid-methyl-β-cyclodextrin (FA-MβCD)/adamantane-albumin exhibit enhanced antitumor activity as compared to FA-MβCD alone.

Supramolecular drug carriers are a promising approach for delivering anticancer drugs with high blood retention after administration. We previously synthesized folic acid-modified methyl-β-cyclodextrin (FA-MβCD) as an anticancer drug. FA-MβCD has a selective autophagy-mediated antitumor effect on folic acid receptor (FR)-expressing cancer cells. Here, we enhanced the antitumor effect and safety of FA-MβCD by preparing a supramolecular nanoparticle formulation of FA-MβCD via host-guest interactions using an adamantane conjugate with human serum albumin (Ad-HSA). The Ad-HSA/FA-MβCD supramolecular complex prolonged the blood retention of FA-MβCD and improved its antitumor effect and safety after intravenous administration in tumor-bearing mice xenografted with FR-expressing cancer cells. These results suggest that the supramolecular technique using Ad-HSA is a promising approach for the delivery of CD-based anticancer drugs.