Abstract
Epigenetic modifications regulate gene expression at the transcriptional level, contributing to tumorigenesis and progression. While epigenetic-targeted combination therapies have gained prominence in oncology treatment management, their clinical efficacy remains constrained by differences in pharmacokinetics and biodistribution among combined agents. Nano-drug delivery systems (NDDS) demonstrate unique potential through co-delivery of therapeutic agents and optimization of their pharmacokinetic profiles. Furthermore, the development of multifunctional NDDS opens new possibilities for precision modulation in cancer treatment, offering valuable insights for clinical translation. Here, this review first outlined the intervention mechanisms of epigenetic dysregulation and analyzed the applications of epigenetic combination approaches. Subsequently, we highlight the transformative potential of NDDS in epigenetic combination therapy, with particular emphasis on how multifunctional NDDS design enables precise therapeutic regulation. This comprehensive analysis aims to advance the clinical translation of epigenetic-based combination strategies through innovative drug delivery solutions. In the future, with the continuous development of AI-driven NDDS design, biomimetic carriers, and dynamic epigenetic editing tools, it will be possible to overcome the clinical challenges of NDDS, enabling truly personalized cancer treatment.