Recent advances in nanomedicines loaded with MicroRNAs for cancer demethylation therapy

DNA methylation constitutes an important form of epigenetic modification that can regulate gene expression through the addition of methyl groups to specific positions on the DNA molecule without modifying the DNA sequence. High levels of DNA methylation have been implicated in the progression of cancer; thus, demethylation therapy can be considered a potential therapeutic strategy. MicroRNAs (miRNAs), essential epigenetic regulators, play pivotal roles in cancer development. In DNA demethylation therapy, miRNAs can regulate DNA methylation-related proteins to reduce or reverse DNA methylation levels and restore normal gene expression. Nanomaterials possess distinctive physicochemical properties that facilitate the efficient delivery of miRNAs to target cells. Through the optimization of the surface properties and structure of nanomaterials, their loading capacity and delivery efficiency of miRNAs can be further enhanced. Recently, nanomedicines loaded with miRNAs have been continuously developed for cancer demethylation therapy. Herein, we concisely review the relationship between miRNAs and cancer DNA methylation, the mechanisms of cancer DNA methylation, and the advances in cancer DNA demethylation treatment for nanomedicines loaded with miRNAs, with the intent of offering novel insights into cancer demethylation therapy. • The latest cancer demethylation therapies involving miRNA-based nanomedicines are reviewed. • miRNAs can target DNA methylation-associated proteins or signaling pathways. • miRNAs regulate the level of DNA methylation either directly or indirectly. • The challenges of using miRNA nanomedicines for cancer demethylation therapy are discussed.