PMID- 26556288 OWN - NLM STAT- MEDLINE DCOM- 20160926 LR - 20151216 IS - 1944-8252 (Electronic) IS - 1944-8244 (Linking) VI - 7 IP - 49 DP - 2015 Dec 16 TI - Bioinert Anodic Alumina Nanotubes for Targeting of Endoplasmic Reticulum Stress and Autophagic Signaling: A Combinatorial Nanotube-Based Drug Delivery System for Enhancing Cancer Therapy. PG - 27140-51 LID - 10.1021/acsami.5b07557 [doi] AB - 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. FAU - Wang, Ye AU - Wang Y AD - School of Chemical Engineering and double daggerDiscipline of Surgery, Basil Hetzel Institute, The University of Adelaide , Adelaide, South Australia 5005, Australia. FAU - Kaur, Gagandeep AU - Kaur G AD - School of Chemical Engineering and double daggerDiscipline of Surgery, Basil Hetzel Institute, The University of Adelaide , Adelaide, South Australia 5005, Australia. FAU - Chen, Yuting AU - Chen Y AD - School of Chemical Engineering and double daggerDiscipline of Surgery, Basil Hetzel Institute, The University of Adelaide , Adelaide, South Australia 5005, Australia. FAU - Santos, Abel AU - Santos A AD - School of Chemical Engineering and double daggerDiscipline of Surgery, Basil Hetzel Institute, The University of Adelaide , Adelaide, South Australia 5005, Australia. FAU - Losic, Dusan AU - Losic D AD - School of Chemical Engineering and double daggerDiscipline of Surgery, Basil Hetzel Institute, The University of Adelaide , Adelaide, South Australia 5005, Australia. FAU - Evdokiou, Andreas AU - Evdokiou A AD - School of Chemical Engineering and double daggerDiscipline of Surgery, Basil Hetzel Institute, The University of Adelaide , Adelaide, South Australia 5005, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151201 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 RN - 333DO1RDJY (Serotonin) RN - 7440-57-5 (Gold) RN - LMI26O6933 (Aluminum Oxide) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Aluminum Oxide/*chemistry MH - Animals MH - Autophagy MH - Catalysis MH - Dopamine/metabolism MH - Endoplasmic Reticulum Stress/physiology MH - Gold/*chemistry MH - Humans MH - Metal Nanoparticles/*chemistry MH - Nanotubes/*chemistry MH - Serotonin/metabolism MH - Signal Transduction/physiology OTO - NOTNLM OT - anodic alumina nanotubes OT - autophagy OT - cell signaling OT - drug delivery OT - endoplasmic reticulum stress OT - nanotoxicity EDAT- 2015/11/12 06:00 MHDA- 2016/09/27 06:00 CRDT- 2015/11/12 06:00 PHST- 2015/11/12 06:00 [entrez] PHST- 2015/11/12 06:00 [pubmed] PHST- 2016/09/27 06:00 [medline] AID - 10.1021/acsami.5b07557 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2015 Dec 16;7(49):27140-51. doi: 10.1021/acsami.5b07557. Epub 2015 Dec 1.