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|Title:||Bioinert anodic alumina nanotubes for targeting of endoplasmic reticulum stress and autophagic signaling: a combinatorial nanotube-based drug delivery system for enhancing cancer therapy|
|Citation:||ACS Applied Materials and Interfaces, 2015; 7(49):27140-27151|
|Publisher:||American Chemical Society|
|Ye Wang, Gagandeep Kaur, Yuting Chen, Abel Santos, Dusan Losic, and Andreas Evdokiou|
|Abstract:||Although nanoparticle-based targeted delivery systems have gained promising achievements for cancer therapy, the development of sophisticated strategies with effective combinatorial therapies remains an enduring challenge. Herein, we report the fabrication of a novel nanomaterial, so-called anodic alumina nanotubes (AANTs) for proof-of-concept cancer therapy by targeting cell signaling networks. This strategy is to target autophagic and endoplasmic reticulum (ER) stress signaling by using thapsigargin (TG)-loaded AANTs cotreated with an autophagy inhibitor 3-methyladenine (3-MA). We first show that AANTs are nontoxic and can activate autophagy in different cell types including human fibroblast cells (HFF), human monocyte cells (THP-1), and human breast cancer cells (MDA-MB 231-TXSA). Treatment with 3-MA at a nontoxic dose reduced the level of autophagy induced by AANTs, and consequently sensitized breast cancer cells to AANTs-induced cellular stresses. To target autophagic and ER stress signaling networking, breast cancer cells were treated with 3-MA together with AANTs loaded with the prototype ER stress inducer TG. We demonstrated that 3-MA enhanced the cancer cell killing effect of AANTs loaded with TG. This effect was associated with enhanced ER stress signaling due to the combination effect of TG and 3-MA. These findings not only demonstrate the excellent biocompatibility of AANTs as novel biomaterials but also provide new opportunities for developing ER- and autophagy-targeted delivery systems for future clinical cancer therapy.|
|Keywords:||anodic alumina nanotubes|
endoplasmic reticulum stress
|Rights:||© 2015 American Chemical Society|
|Appears in Collections:||Aurora harvest 3|
Chemical Engineering publications
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