Selective ablation of β-galactosidase-expressing cells with a rationally designed activatable photosensitizer.
We have developed an activatable photosensitizer capable of specifically inducing the death of β-galactosidase-expressing cells in response to photoirradiation. By using a selenium-substituted rhodol scaffold bearing β-galactoside as a targeting substituent, we designed and synthesized HMDESeR-βGal, which has a non-phototoxic spirocyclic structure owing to the presence of the galactoside moiety. However, β-galactosidase efficiently converted HMDESeR-βGal into phototoxic HMDESeR, which exists predominantly in the open xanthene form. This structural change resulted in drastic recovery of visible-wavelength absorption and the ability to generate singlet oxygen ((1)O2). When HMDESeR-βGal was applied to larval Drosophila melanogaster wing disks, which express β-galactosidase only in the posterior region, photoirradiation induced cell death in the β-galactosidase-expressing region with high specificity.
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
Yuki
Y
Ichikawa
Mako
M
Kamiya
Fumiaki
F
Obata
Masayuki
M
Miura
Takuya
T
Terai
Toru
T
Komatsu
Tasuku
T
Ueno
Kenjiro
K
Hanaoka
Tetsuo
T
Nagano
Yasuteru
Y
Urano
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004331:Drosophila melanogaster / Q000254:growth & development; D005456:Fluorescent Dyes / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007814:Larva / Q000254:growth & development; D007834:Lasers; D017319:Photosensitizing Agents / Q000737:chemistry / Q000633:toxicity; D012643:Selenium / Q000737:chemistry; D018036:Selenium Compounds / Q000737:chemistry* / Q000633:toxicity; D026082:Singlet Oxygen / Q000378:metabolism; D013816:Thermodynamics; D014921:Wings, Animal / Q000187:drug effects / Q000254:growth & development; D001616:beta-Galactosidase / Q000737:chemistry / Q000378:metabolism*
D005456:Fluorescent Dyes; C000597355:HMDESeR; D017319:Photosensitizing Agents; D018036:Selenium Compounds; D026082:Singlet Oxygen; D001616:beta-Galactosidase; D012643:Selenium
activatable photosensitizers; cell ablation; fluorescent probes; intramolecular spirocyclization; selenium