Integrating Epigenetic Modulators in Nanofibers for Synergistic Gastric Cancer Therapy via Epigenetic Reprogramming

Area of Science:

• Oncology
• Nanotechnology
• Epigenetics

Background:

• Epigenetic dysregulation is a hallmark of cancer and a target for therapy.
• Current epigenetic drugs face challenges in specificity, stability, and tumor retention for solid tumors.

Purpose of the Study:

• To develop a combinatorial drug delivery system for epigenetic modulatory drugs.
• To enhance the stability and tumor targeting of epigenetic therapies for gastric cancer.

Main Methods:

• Utilized molecular self-assembly to create drug-drug conjugates of DNA methyltransferase and histone deacetylase inhibitors.
• Formulated conjugates into nanofibers with improved chemical stability.
• Investigated the synergistic effects of combined epigenetic drugs on cancer cells and in vivo models.

Main Results:

• The self-assembled nanofibers demonstrated enhanced chemical stability.
• Nanofibers synergistically regulated DNA methylation and histone deacetylation, reprogramming gene expression.
• Significant inhibition of gastric cancer cell proliferation and promotion of apoptosis were observed.
• Superior in vivo therapeutic efficacy was attributed to prolonged tumor retention and reduced off-target effects.

Conclusions:

• Epigenetic-drug-based nanofibers offer a promising strategy for cancer therapy.
• This approach provides a valuable paradigm for epigenetic reprogramming in cancer treatment.
• The developed formulation overcomes limitations of conventional epigenetic drugs in solid tumors.