Pronounced induction of endoplasmic reticulum stress and tumor suppression by surfactant-free poly(lactic-co-glycolic acid) nanoparticles via modulation of the PI3K signaling pathway

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)

摘要

Background: LY294002 (LY) is a potent inhibitor of phosphatidylinositol 3-kinases (PI3Ks); however, biological applications of LY are limited by its poor solubility and pharmacokinetic profile. This study aimed at developing LY-loaded surfactant-free poly(lactic-co-glycolic acid) (PLGA) nanoparticles (SF-LY NPs) to improve the therapeutic effcacy of LY. Materials and methods: Cellular viability was measured by MTT assay. The subcellular distribution of NPs was studied using an ultraviolet-visible spectrophotometer and confocal microscope. The expression of cell-death-associated proteins was determined using Western blotting and the in vivo activity of SF-LY NPs was tested in a xenograft animal model. Results: SF-LY NPs enhanced the intracellular level of LY, induced sustained suppression of AKT, and induced marked cancer cell death. In addition, SF-LY NPs tended to accumulate in the endoplasmic reticulum (ER) and induce pronounced ER stress. Finally, SF-LY NPs exhibited a prominent antitumor effect in vivo. Conclusion: The surfactant-free formulation of PLGA is critical to the promising anticancer activity of SF-LY NPs.

原文English
頁(從 - 到)2689-2706
頁數18
期刊International journal of nanomedicine
8
DOIs
出版狀態Published - 2013

All Science Journal Classification (ASJC) codes

  • 生物物理學
  • 生物工程
  • 生物材料
  • 藥學科學
  • 藥物發現
  • 有機化學

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