Molecules, Vol. 29, Pages 1709: Diselenide-Bridged Doxorubicin Dimeric Prodrug: Synthesis and Redox-Triggered Drug Release

Molecules, Vol. 29, Pages 1709: Diselenide-Bridged Doxorubicin Dimeric Prodrug: Synthesis and Redox-Triggered Drug Release
Molecules doi: 10.3390/molecules29081709
Authors:
Yanru Hu
Peng Liu

The diselenide bond has attracted intense interest in redox-responsive drug delivery systems (DDSs) in tumor chemotherapy, due to its higher sensitivity than the most investigated bond, namely the disulfide bond. Here, a diselenide-bridged doxorubicin dimeric prodrug (D-DOXSeSe) was designed by coupling two doxorubicin molecules with a diselenodiacetic acid (DSeDAA) molecule via α-amidation, as a redox-triggered drug self-delivery system (DSDS) for tumor-specific chemotherapy. The drug release profiles indicated that the D-DOXSeSe could be cleaved to release the derivatives selenol (DOX-SeH) and seleninic acid (DOX-SeOOH) with the triggering of high GSH and H2O2, respectively, indicating the double-edged sword effect of the lower electronegativity of the selenide atom. The resultant solubility-controlled slow drug release performance makes it a promising candidate as a long-acting DSDS in future tumor chemotherapy. Moreover, the interaction between the conjugations in the design of self-immolation traceless linkers was also proposed for the first time as another key factor for a desired precise tumor-specific chemotherapy, besides the conjugations themselves.

Source: Molecules - April 10, 2024 Category: Chemistry Authors: Yanru Hu Peng Liu Tags: Article Source Type: research