Abstract

Epigenetic dysregulation is a defining feature of cancer, driving malignant transformation, tumor progression, 
and therapeutic resistance through reversible yet heritable alterations in gene expression. Aberrant DNA 
methylation, histone modifications, and chromatin remodeling disrupt normal cellular identity and enable 
oncogenic transcriptional programs without altering the underlying DNA sequence. Although epigenetic 
enzymes are druggable and several epigenetic inhibitors have reached clinical use, their therapeutic impact has 
been constrained by limited specificity, systemic toxicity, poor pharmacokinetics, and the inability to precisely 
modulate complex epigenetic networks within tumors. Nanotechnology-based strategies have emerged as 
powerful tools to address these limitations by enabling targeted delivery, controlled release, and combinatorial 
modulation of epigenetic regulators. By leveraging nanoscale materials such as liposomes, polymeric 
nanoparticles, inorganic nanocarriers, and self-assembled systems, epigenetic drugs can be selectively delivered 
to tumor cells and subcellular compartments, enhancing efficacy while minimizing off-target effects. This review 
provides a comprehensive overview of nanotechnology-based approaches for modulating epigenetic 
dysregulation in cancer. We examine the biological basis of epigenetic alterations in malignancy, discuss major 
nanocarrier platforms for epigenetic therapy, and highlight advances in targeting DNA methylation, histone 
modifications, and chromatin architecture. Current challenges, translational considerations, and future 
directions for precision epigenetic nanomedicine are also critically discussed.