PLGA-PEG nano-delivery system for epigenetic therapy

Asia Naz, Yi Cui, Christopher J. Collins, David H. Thompson, Joseph Irudayaraj

Research output: Contribution to journalArticlepeer-review


Efficient delivery of cytidine analogues such as Azacitidine (AZA) into solid tumors constitutes a primary challenge in epigenetic therapies. We developed a di-block nano-vector based on poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) for stabilization of the conjugated AZA under physiological conditions. With equimolar drug content, our nano-conjugate could elicit a better anti-proliferative effect over free drug in breast cancer both in vitro and in vivo, through reactivation of p21 and BRCA1 to restrict cell proliferation. In addition, we applied single-molecule fluorescence tools to characterize the intracellular behavior of the AZA-PLGE-PEG nano-micelles at a finer spatiotemporal resolution. Our results suggest that the nano-micelles could effectively enrich in cancer cells and may not be limited by nucleoside transporters. Afterwards, the internalized nano-micelles exhibit pH-dependent release and resistance to active efflux. Altogether, our work describes a delivery strategy for DNA demethylating agents with nanoscale tunability, providing a cost-effective option for pharmaceutics.

Original languageEnglish (US)
Pages (from-to)586-597
Number of pages12
JournalBiomedicine and Pharmacotherapy
StatePublished - Jun 1 2017
Externally publishedYes


  • Azacitidine
  • DNA methylation
  • Drug delivery
  • Nanomedicine
  • Single-molecule fluorescence

ASJC Scopus subject areas

  • Pharmacology


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