Nanotechnology-Driven Epigenetic Targeting: Tailoring Ovarian Cancer Therapeutics

Epigenetic mechanisms play a crucial role in OC drug resistance, and emerging evidence suggests that dysregulated epigenetic modifications are among the key contributors to OC. Epigenetic agents, including DNA methyltransferase inhibitors, histone deacetylase inhibitors, and non-coding RNA-based therapeutics, have important limitations, including poor water solubility, limited tissue distribution, low stability, and systemic toxicity. To overcome this, a novel drug delivery system is needed to manage variability in drug administration and maximize the efficacy of these drugs. In this regard, nanotechnology offers an attractive option for formulating epigenetic drugs with various encapsulation strategies to increase bioavailability and drug efficacy, reduce drug dose, administration frequency, and toxicity, and enhance cellular internalization and tumor-targeted delivery. In this review, we summarize various epigenetic regulators and their roles in OC therapy resistance as well as the development of nanosystems for epigenetic drug delivery, which could lay the foundation for designing nanoformulations encapsulating epigenetic therapeutics, ultimately advancing personalized, targeted therapy for patients with OC. This review also discusses the current clinical status of nanocarrier platforms and translational barriers that limit the clinical development of epigenetic nanomedicine, highlighting the future directions required for successful clinical translation.