Biomaterials 35 (2014) 5517e5526
Contents lists available at ScienceDirect
Biomaterials journal homepage: www.elsevier.com/locate/biomaterials
Structurally engineered anodic alumina nanotubes as nano-carriers for delivery of anticancer therapeutics Ye Wang a, Abel Santos a, Gagandeep Kaur a, Andreas Evdokiou b, *, Dusan Losic a, * a b
School of Chemical Engineering, The University of Adelaide, Adelaide, SA 5005, Australia School of Medicine, Discipline of Surgery, The University of Adelaide, Adelaide, SA 5005, Australia
a r t i c l e i n f o
a b s t r a c t
Article history: Received 31 January 2014 Accepted 21 March 2014 Available online 14 April 2014
Here, we report a study on the biocompatibility, cell uptake and in vitro delivery of tumor necrosis factorrelated apoptosis-inducing ligand (Apo2L/TRAIL) by new nano-carriers called anodic alumina nanotubes (AANTs) for potential cancer therapy. AANTs were electrochemically engineered by a unique pulse anodization process, which enables precise control of the nanotube geometry, and used here as nanocarriers for drug delivery. In vitro cytotoxicity and cell uptake of AANTs was assessed using MDAMB231-TXSA human breast cancer cells and mouse RAW 264.7 macrophage cells. AANTs exhibited excellent biocompatibility in both cell lines over a time course of five days even at a maximum concentration of AANTs of 100 mg mL1. Transmission electron microscopy and fluorescence microscopy confirmed a significant uptake of AANTs by RAW 264.7 cells and breast cancer cells. AANTs loaded with the pro-apoptotic protein Apo2L/TRAIL showed exceptional loading capacity (104 14.4 mg mg1 of AANTs) and demonstrated significant decrease in viability of MDA-MB231-TXSA cancer cells due to apoptosis induction. These results demonstrate that AANTs are promising nano-carriers for drug delivery applications. Crown Copyright Ó 2014 Published by Elsevier Ltd. All rights reserved.
Keywords: Tumor necrosis factor-related apoptosisinducing ligand (TRAIL) Anodic alumina nanotubes Breast cancer Protein/drug delivery
1. Introduction Delivery of bioactive drugs such as proteins and nucleic acids for cancer therapy has long faced great challenges mainly due to their poor pharmacokinetics, kidney or liver clearance and low permeability across intracellular barriers [1,2]. Rapid advances in developing nanomaterials for therapeutic drug delivery have brought new opportunities to overcome these inherent drawbacks. Their unique properties such as selective tumor targeting, limited side effects, co-delivery of different drugs, protection by encapsulation and controlled pharmacokinetics under physiological conditions make them suitable candidates for drug delivery applications [3]. For instance, Apo2L/TRAIL is a pro-apoptotic receptor agonist that belongs to the tumor necrosis factor (TNF) family of death ligands and can induce apoptosis of cancer cells with limited or no toxicity to normal cells [4]. Previous studies have demonstrated that Apo2L/TRAIL has a remarkable antitumor capability itself and a synergistic antitumor effect when combined with other chemotherapeutic agents [5,6]. However, poor pharmacokinetics (
Contents lists available at ScienceDirect
Biomaterials journal homepage: www.elsevier.com/locate/biomaterials
Structurally engineered anodic alumina nanotubes as nano-carriers for delivery of anticancer therapeutics Ye Wang a, Abel Santos a, Gagandeep Kaur a, Andreas Evdokiou b, *, Dusan Losic a, * a b
School of Chemical Engineering, The University of Adelaide, Adelaide, SA 5005, Australia School of Medicine, Discipline of Surgery, The University of Adelaide, Adelaide, SA 5005, Australia
a r t i c l e i n f o
a b s t r a c t
Article history: Received 31 January 2014 Accepted 21 March 2014 Available online 14 April 2014
Here, we report a study on the biocompatibility, cell uptake and in vitro delivery of tumor necrosis factorrelated apoptosis-inducing ligand (Apo2L/TRAIL) by new nano-carriers called anodic alumina nanotubes (AANTs) for potential cancer therapy. AANTs were electrochemically engineered by a unique pulse anodization process, which enables precise control of the nanotube geometry, and used here as nanocarriers for drug delivery. In vitro cytotoxicity and cell uptake of AANTs was assessed using MDAMB231-TXSA human breast cancer cells and mouse RAW 264.7 macrophage cells. AANTs exhibited excellent biocompatibility in both cell lines over a time course of five days even at a maximum concentration of AANTs of 100 mg mL1. Transmission electron microscopy and fluorescence microscopy confirmed a significant uptake of AANTs by RAW 264.7 cells and breast cancer cells. AANTs loaded with the pro-apoptotic protein Apo2L/TRAIL showed exceptional loading capacity (104 14.4 mg mg1 of AANTs) and demonstrated significant decrease in viability of MDA-MB231-TXSA cancer cells due to apoptosis induction. These results demonstrate that AANTs are promising nano-carriers for drug delivery applications. Crown Copyright Ó 2014 Published by Elsevier Ltd. All rights reserved.
Keywords: Tumor necrosis factor-related apoptosisinducing ligand (TRAIL) Anodic alumina nanotubes Breast cancer Protein/drug delivery
1. Introduction Delivery of bioactive drugs such as proteins and nucleic acids for cancer therapy has long faced great challenges mainly due to their poor pharmacokinetics, kidney or liver clearance and low permeability across intracellular barriers [1,2]. Rapid advances in developing nanomaterials for therapeutic drug delivery have brought new opportunities to overcome these inherent drawbacks. Their unique properties such as selective tumor targeting, limited side effects, co-delivery of different drugs, protection by encapsulation and controlled pharmacokinetics under physiological conditions make them suitable candidates for drug delivery applications [3]. For instance, Apo2L/TRAIL is a pro-apoptotic receptor agonist that belongs to the tumor necrosis factor (TNF) family of death ligands and can induce apoptosis of cancer cells with limited or no toxicity to normal cells [4]. Previous studies have demonstrated that Apo2L/TRAIL has a remarkable antitumor capability itself and a synergistic antitumor effect when combined with other chemotherapeutic agents [5,6]. However, poor pharmacokinetics (
