Synthesis and photocleavage of a new polymerizable [2+2] hetero dimer for phototriggered drug delivery

7-Hydroxy-1,1-dimethylnaphtalenone is introduced as a versatile photocleavable linker system for drug attachment to polymer materials with significantly improved two-photon-absorption efficiency. The synthesis of TBDMS-protected 7-hydroxy-1,1-dimethylnaphtalenone monomer is described, which is the release group attached to the polymer moiety. The cytotoxic 5-fluoro-1-heptanoyluracil was photochemically attached via [2+2] cycloaddition to this release group. The linker–drug conjugate was photochemically polymerized into a HEMA/MMA copolymer. Photo-triggered drug release from the polymer via single-photon-absorption as well as two-photon-absorption in solution were carried out. The detachment of 5-FU from the polymer and its release from the polymer were monitored in the polymer as well as in the aqueous medium and multidose drug release was successfully demonstrated.