PLGA-PEG nano-delivery system for epigenetic therapy

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

Research output: Contribution to journalArticle

Abstract

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
Volume90
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Fingerprint

Azacitidine
Ethylene Glycol
Micelles
Epigenomics
Nucleoside Transport Proteins
Pharmaceutical Preparations
Cytidine
Neoplasms
Therapeutics
Fluorescence
Cell Proliferation
Breast Neoplasms
Costs and Cost Analysis
DNA
polylactic acid-polyglycolic acid copolymer

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

PLGA-PEG nano-delivery system for epigenetic therapy. / Naz, Asia; Cui, Yi; Collins, Christopher J.; Thompson, David H.; Irudayaraj, Joseph Maria Kumar.

In: Biomedicine and Pharmacotherapy, Vol. 90, 01.06.2017, p. 586-597.

Research output: Contribution to journalArticle

Naz, Asia ; Cui, Yi ; Collins, Christopher J. ; Thompson, David H. ; Irudayaraj, Joseph Maria Kumar. / PLGA-PEG nano-delivery system for epigenetic therapy. In: Biomedicine and Pharmacotherapy. 2017 ; Vol. 90. pp. 586-597.
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