Poly(vinyl alcohol) potentiating an inert d-amino acid-based drug for boron neutron capture therapy

• DOI: 10.1016/j.jconrel.2024.11.017
• Publication Date: 2024-12-03T20:15:41Z
• Authors: Kakeru Konarita; Kaito Kanamori; Minoru Suzuki; Daiki Tokura; Shota Tanaka; Yuto Honda; Nobuhiro Nishiyama; Takahiro Nomoto
• Keywords: Boron neutron capture therapy; 570; Poly(vinyl alcohol); Amino acid transporter; Polymer-drug conjugates

「液体のり」の成分と「鏡」を利用したがん治療 --ポリビニルアルコールが“役に立たない”化合物に秘められた効果を引き出す--. 京都大学プレスリリース. 2024-12-04. ; Since the discovery of d-amino acids, they have been considered inactive and have not been used as potent drugs. Here, we report that simple mixing with poly(vinyl alcohol) (PVA) unleashed latent potentials of d-amino acids in boron neutron capture therapy (BNCT). PVA formed boronate esters with seemingly useless boronated d-amino acids and induced tumor-associated amino acid transporter-superselective internalization and prolonged intracellular retention, accomplishing complete cure of tumors. The superselective internalization was achieved by switching the internalization pathway from ineffective pass through the transporter to the transporter-mediated endocytosis. The acidic environment in the endo-/lysosome dissociated the boronate esters and elicited the stealthiness of the drugs, preventing their externalization and prolonging intracellular retention time. In a subcutaneous tumor model, this system accomplished surprisingly high tumor-selective accumulation that could not be achieved by conventional approaches and induced drastic BNCT effects. PVA may be a unique material to unlock potentials of seemingly inert molecules.