Nanoparticles of folic acid‐methyl‐β‐cyclodextrin (FA‐MβCD)/adamantane‐albumin exhibit enhanced antitumor activity compared with 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. A supramolecular nanoparticle formulation of folic acid‐modified methyl‐β‐cyclodextrin (FA‐MβCD) by host–guest interactions using an adamantane conjugate with human serum albumin (Ad‐HSA). The Ad‐HSA/FA‐MβCD supramolecular complex significantly prolonged the blood retention of FA‐MβCD and improved its antitumor effect and safety after intravenous administration in tumor‐bearing nude mice xenografted with FR‐expressing cancer cells.