Daunorubicin Citrate

Daunorubicin citrate exerts its anticancer activity primarily through intercalation into DNA and inhibition of topoisomerase II. By inserting its planar ring structure between adjacent DNA base pairs, daunorubicin disrupts the normal helical structure and blocks the progression of topoisomerase II, an enzyme responsible for relaxing DNA supercoils during replication and transcription. The drug stabilizes the topoisomerase II-DNA covalent complex after double-strand break induction, preventing DNA religation and leading to persistent DNA strand breaks that trigger apoptosis. In addition to these canonical mechanisms, daunorubicin also induces NF-κB DNA-binding activity while simultaneously repressing NF-κB-dependent transcription, a functional profile distinct from other topoisomerase II inhibitors such as etoposide. Furthermore, daunorubicin undergoes redox cycling to generate oxygen free radicals, which contributes to both its cytotoxic effects and its dose-limiting cardiotoxicity.

Fig. 1 Different characteristics of the compounds used in this study and their effect on NF-κB. (Campbell K J.; et al. 2006)

A micellar nanocomplex was self-assembled from daunorubicin and epigallocatechin gallate (EGCG) without the use of any carrier materials. The nanocomplex remained stable at physiological pH 7.4 but rapidly released daunorubicin at acidic pH 5.5, mimicking the endosomal environment. Compared to free daunorubicin, the nanocomplex exhibited superior cytotoxic efficacy against multidrug-resistant human leukemia cells through strong synergistic action. The enhanced efficacy was associated with increased nuclear accumulation of daunorubicin, elevated intracellular reactive oxygen species levels, and enhanced caspase-mediated apoptosis induction. This carrier-free nanocomplex strategy effectively circumvented chemoresistance in acute myeloid leukemia treatment.

Fig. 2 Dauno-MNC via self-assembly of DNR and HA-EGCG conjugate and acid-triggered DNR release. (Bae K H.; et al. 2022)