期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 90, 期 -, 页码 586-597出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2017.03.093
关键词
Azacitidine; Nanomedicine; Drug delivery; DNA methylation; Single-molecule fluorescence
资金
- HEC Pakistan training grant
- W.M. Keck Foundation
- Purdue Center for Cancer Research [P30CA023168]
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. (C) 2017 Elsevier Masson SAS. All rights reserved.
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