Nanotechnology-Based Strategies for Modulating Epigenetic Dysregulation in Cancer

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. Keywords: epigenetic therapy; nanotechnology; cancer; chromatin regulation; precision oncology.