Bioinert Anodic Alumina Nanotubes for Targeting of Endoplasmic Reticulum Stress and Autophagic Signaling: A Combinatorial Nanotube-Based Drug Delivery System for Enhancing Cancer Therapy.

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.

• Authors: Ye Wang, Gagandeep Kaur, Yuting Chen, Abel Santos, Dusan Losic, Andreas Evdokiou
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 7 Issue 49 Pg. 27140-51 (Dec 16 2015) ISSN: 1944-8252 [Electronic] United States
• PMID: 26556288 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Serotonin
• Gold
• Aluminum Oxide
• Dopamine

Topics

• Aluminum Oxide (chemistry)
• Animals
• Autophagy
• Catalysis
• Dopamine (metabolism)
• Endoplasmic Reticulum Stress (physiology)
• Gold (chemistry)
• Humans
• Metal Nanoparticles (chemistry)
• Nanotubes (chemistry)
• Serotonin (metabolism)
• Signal Transduction (physiology)