title: Systematic in vitro nanotoxicity study on anodic alumina nanotubes with engineered aspect ratio: understanding nanotoxicity by a nanomaterial model.
abstract: Here, we report a detailed and systematic approach for studying the in vitro nanotoxicity study of high aspect ratio (HAR) nanomaterials using anodic alumina nanotubes (AANTs) as a nanomaterial model. AANTs with bio-inert properties and tailored aspect ratios ranging from 7.8 to 63.3 were synthesized by an electrochemical pulse anodization process. Cytotoxicity studies were conducted with RAW 264.7 mouse macrophage cells and MDA-MB 231-TXSA human breast cancer cells through several toxicity parameters, including cell viability and morphology, pro-inflammatory response, mitochondrial depolarization, lysosomal membrane permeabilization (LMP), induction of autophagy and endoplasmic reticulum (ER) stress. The resulting toxicity patterns were cell-type dependent and strongly related with AANTs dose, length of time, and importantly the AR of AANTs. Long AANTs triggered enhanced cell death, morphological changes, tumor necrosis factor α (TNF-α) release, LMP and ER stress than short AANTs. The toxic AR window of AANTs was determined to be 7.8, which is shorter than that of other previously reported HAR nanomaterials. This toxic AR window provides a promising opportunity to control the nanotoxicity of HAR nanomaterials for their advanced drug delivery application.
authors: School of Chemical Engineering, The University of Adelaide, Adelaide, SA 5005, Australia; Discipline of Surgery, Basil Hetzel Institute, The University of Adelaide, Adelaide, SA 5005, Australia.
authors: Ye
authors: Y
authors: Wang
authors: School of Chemical Engineering, The University of Adelaide, Adelaide, SA 5005, Australia; Discipline of Surgery, Basil Hetzel Institute, The University of Adelaide, Adelaide, SA 5005, Australia.
authors: Gagandeep
authors: G
authors: Kaur
authors: Discipline of Surgery, Basil Hetzel Institute, The University of Adelaide, Adelaide, SA 5005, Australia.
authors: Aneta
authors: A
authors: Zysk
authors: Discipline of Surgery, Basil Hetzel Institute, The University of Adelaide, Adelaide, SA 5005, Australia.
authors: Vasilios
authors: V
authors: Liapis
authors: Discipline of Surgery, Basil Hetzel Institute, The University of Adelaide, Adelaide, SA 5005, Australia.
authors: Shelley
authors: S
authors: Hay
authors: School of Chemical Engineering, The University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: abel.santos@adelaide.edu.au.
authors: Abel
authors: A
authors: Santos
authors: School of Chemical Engineering, The University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: dusan.losic@adelaide.edu.au.
authors: Dusan
authors: D
authors: Losic
authors: Discipline of Surgery, Basil Hetzel Institute, The University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: andreas.evdokiou@adelaide.edu.
authors: Andreas
authors: A
authors: Evdokiou
mesh_terms: D000537:Aluminum Oxide / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D004566:Electrodes; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity*; D036103:Nanotechnology / Q000379:methods*; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010539:Permeability; D017382:Reactive Oxygen Species / Q000378:metabolism; D012996:Solutions; D055672:Static Electricity; D018675:Toxicity Tests
chemical_list: D017382:Reactive Oxygen Species; D012996:Solutions; D000537:Aluminum Oxide
keywords: Anodic alumina nanotubes; Apoptosis; Aspect ratio; Endoplasmic reticulum stress; Lysosome injury; Nanotoxicity