Sterically Controlled Cyclobutane-Dioxetane Ultrabright Afterglow Nanosystem for Cyclic Therapy of Choroidal Neovascularization in Mice DOI
Jia‐Wei Zhang, Haoliang Shi, Xuan Qin

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

Afterglow occurring after light excitation ceases offers a safer source to the laser-activated verteporfin therapy approved by FDA for choroidal neovascularization (CNV). However, conventional afterglow molecules, especially adamantane-dioxetanes with high steric hindrance, exhibit limited chemiexcitation, restricting electron transfer and diminishing therapeutic effects. Here, we constructed ultrabright nanosystems integrating low-hindrance cyclobutane moieties into dioxetane framework. Among these substituents, benzyl oxocyclobutane-dioxetane is brightest molecule due its lowest showing 35.7 times faster relative chemiexcitation rate 59 higher intensity than adamantane-dioxetane, alongside three-order-of-magnitude increase in total emission. Consequently, at equivalent concentration, oxocyclobutane-dioxetane-based nanosystem produces nearly five more singlet oxygen free verteporfin. In CNV mouse model, cyclic treatment our reduced lesion areas 64.9%, outperforming 39.3% reduction achieved counterpart. By eliminating need laser activation, this strategy minimizes ocular damage, providing safe effective other retinal disorders.

Language: Английский

Sterically Controlled Cyclobutane-Dioxetane Ultrabright Afterglow Nanosystem for Cyclic Therapy of Choroidal Neovascularization in Mice DOI
Jia‐Wei Zhang, Haoliang Shi, Xuan Qin

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

Afterglow occurring after light excitation ceases offers a safer source to the laser-activated verteporfin therapy approved by FDA for choroidal neovascularization (CNV). However, conventional afterglow molecules, especially adamantane-dioxetanes with high steric hindrance, exhibit limited chemiexcitation, restricting electron transfer and diminishing therapeutic effects. Here, we constructed ultrabright nanosystems integrating low-hindrance cyclobutane moieties into dioxetane framework. Among these substituents, benzyl oxocyclobutane-dioxetane is brightest molecule due its lowest showing 35.7 times faster relative chemiexcitation rate 59 higher intensity than adamantane-dioxetane, alongside three-order-of-magnitude increase in total emission. Consequently, at equivalent concentration, oxocyclobutane-dioxetane-based nanosystem produces nearly five more singlet oxygen free verteporfin. In CNV mouse model, cyclic treatment our reduced lesion areas 64.9%, outperforming 39.3% reduction achieved counterpart. By eliminating need laser activation, this strategy minimizes ocular damage, providing safe effective other retinal disorders.

Language: Английский

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