Type Of Media：学術論文
Publication/Magazine/Media：Chemical Engineering Journal
Author：Y. Honda, D. Tokura, S. E. Muttaqien, K. Konarita, Y. Kawashima, N. Nishiyama and T. Nomoto
Phenylboronic acid-based polymers exerting intracellular hydrophilic-to-hydrophobic conversion to retain within target cells
Summary:
Many functional polymers have been developed for drug delivery. However, only a few studies focused on improvement of retention within target cells. Here, we report a simple technique to construct polymers that can retain within specific cells by converting their hydrophilic property to hydrophobic. The key to the conversion lies in the side chains having phenylboronic acid moieties, which can accommodate various kinds of polyol molecules through the formation of boronate esters just by mixing in aqueous solution at physiological pH like extracellular environment. The boronate ester formation endowed hydrophilicity to the polymer and simultaneously augmented interaction between the conjugated polyol structures, specifically 3-hydroxy-l-tyrosine (L-DOPA), and tumor-associated amino acid transporters on the cell membrane. The polymer/L-DOPA complex was then taken up by the cell via endocytosis, and acidic endo−/lysosomal environment dissociated the boronate esters, thereby inducing the conversion from the hydrophilic property to hydrophobic. This caused agglomeration of the polymers and exhibited appreciably prolonged intracellular retention. We found that polymers modified with L-DOPA could show tumor-selective interaction and retention in peritoneal tumors, permitting their longitudinal fluorescent detection. Boronic acid chemistry should offer a unique approach to construct polymer-based drug delivery systems for improving retention in target sites.
https://doi.org/10.1016/j.cej.2025.171908
