Intracellular enzyme-activatable prodrug for real-time monitoring of chlorambucil delivery and imagi

来源 :Chinese Chemical Letters | 被引量 : 0次 | 上传用户:gaoyueeryubing
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Carboxylesterase,a necessary enzyme in various mammalian cells,has been employed in various biological applications.Herein,we designed and synthesized a novel carboxylesterase-based prodrug,which can realize simultaneous drug-release imaging and cancer chemotherapy.This prodrug comprises three parts:coumarin as the fluorophore and the cleavable architecture,chlorambucil as the anticancer drug,and acetyl group as the enzyme-responsive unit.The presence of carboxylesterase leads to the activation of coumarin fluorescence,and this fluorescence serves as the reporting signal for assessing the enzyme level and drug release.Moreover,the prodrug was incorporated in liposome for monitoring drug release and chemotherapeutic effect in living cells.Upon internalization by HeLa cells,the prodrug can release chlorambucil and exhibit high cytotoxicity.This approach may provide some helpful insights for enhancing therapeutic effect and tracking the release of prodrug. Carboxylesterase, a necessary enzyme in various mammalian cells, has been employed in various biological applications. Herein, we designed and synthesized a novel carboxylesterase-based prodrug, which can enable simultaneous drug-release imaging and cancer chemotherapy.This prodrug comprises three parts: coumarin as the fluorophore and the cleavable architecture, chlorambucil as the anticancer drug, and acetyl group as the enzyme-responsive unit. The presence of carboxylesterase leads to the activation of coumarin fluorescence, and this fluorescence serves as the reporting signal for assessing the enzyme level and drug release. Moreover, the prodrug was incorporated in liposomes for monitoring drug release and chemotherapeutic effect in living cells. 结 internalization by HeLa cells, the prodrug can release chlorambucil and exhibit high cytotoxicity. This approach may provide some helpful insights for enhancing therapeutic effect and tracking the release of prodrug.
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