Colloids and Surfaces B: Biointerfaces 160 (2017) 1–10 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces journal homepage: www.elsevier.com/locate/colsurfb Protocols Porous NH 2 -MIL-125 as an efficient nano-platform for drug delivery, imaging, and ROS therapy utilized Low-Intensity Visible light exposure system Arunkumar Rengaraj a,1 , Pillaiyar Puthiaraj b,1 , Nam-Su Heo a , Hoomin Lee a , Seung Kyu Hwang a , Soonjo Kwon c , Wha-Seung Ahn b,∗ , Yun-Suk Huh a,∗ a Department of Biological Engineering, Biohybrid Systems Research Center (BSRC), Inha University, Incheon, 22212, Republic of Korea b Department of Chemistry and Chemical Engineering, Inha University, Incheon, 22212, Republic of Korea c Department of Biological Engineering, Integrated Tissue Engineering, Inha University, Incheon, 22212, Republic of Korea a r t i c l e i n f o Article history: Received 24 May 2017 Received in revised form 3 August 2017 Accepted 5 September 2017 Available online 6 September 2017 Keywords: Metal organic frameworks NH2-MIL-125 Doxorubicin Drug delivery ROS therapy a b s t r a c t Metal-organic frameworks are a novel class of organic-inorganic hybrid polymer with potential applica- tions in bioimaging, drug delivery, and ROS therapy. NH 2 -MIL-125, which is a titanium-based metal organic framework with a large surface area of 1540 m 2 /g, was synthesized using a hydrothermal method. The material was characterized by powder X-ray diffreaction (PXRD), thermogravimetric analy- sis (TGA), and transmission electron microscopy (TEM), and N 2 isotherm analyses. The size of the polymer was reduced to the nanoscale using a high-frequency sonication process. PEGylation was carried out to improve the stability and bioavailability of the NMOF. The as-synthesized nano-NH 2 -MIL-125/PEG (NMOF/PEG) exhibited good biocompatibility over the (Cancer) MCF-7 and (Normal) COS-7 cell line. The interaction of NMOF/PEG with the breast cancer cell line (MCF-7) was examined by BIO-TEM analysis and laser confocal imaging. 2 ′ ,7 ′ –dichlorofluorescin diacetate (DCFDA) analysis confirmed that NMOF/PEG produced free radicals inside the cancer cell line (MCF-7) upon visible light irradiation. NMOF/PEG absorbed a large amount of DOX (20 wt.% of DOX) and showed pH, and photosensitive release. This controlled drug delivery was attributed to the presence of NH 2 , Ti group in MOF and a hydroxyl group in PEG. This combination of chemo- and ROS-therapy showed excellent efficiency in killing cancer MCF-7 cells. © 2017 Published by Elsevier B.V. 1. Introduction Cancer is a chronic disease that involves the abnormal evolu- tion of cells with the potential to invade other organs and causes approximately 6 million deaths annually [1]. A report issued by the International Agency for Research on Cancer (IARC) revealed 14.1 million cancer patients around the world in 2012. Of these, 7.4 million and 6.7 million cases were men and women, respectively. In women, breast cancer is the most common cancer with almost 1.7 million new patients diagnosed in 2012 [2]. Most breast can- cers originate in the lobules and ducts that connect the lobules to the nipple [3]. Over the last few years, there has been a significant development in breast cancer treatment but many cases are diag- ∗ Corresponding authors. E-mail addresses: whasahn@inha.ac.kr (W.-S. Ahn), yunsuk.huh@inha.ac.kr (Y.-S. Huh). 1 These authors contributed equally to this work. nosed in the late stage, and multidrug resistance has increased [4]. To solve these problems, a platform that can be used for diagnosis, as well as combined therapy on cancer cells, is needed. Recently, nanotechnology has been used in cancer treatments for more effi- cient early diagnoses, imaging, and targeted therapies [5]. Nanocarriers are important drug-delivery systems that can be used for diagnosis and provide sustainable drug release at the tar- geted sites. Along with drug delivery, these nanomaterials can also be used in combination therapies, such as gene therapy, theranos- tic, and ROS therapy [6–8]. Over the last decade, different kinds of nanocarriers have been demonstrated in drug delivery systems, such as dendrimers, lipids, carbohydrate polymers, polymer-coated metal nanoparticles, activated carbon, zeolites, amine-modified porous silica, metal-organic frameworks (MOFs), and porous cova- lent triazine polymers (CTPs) [9–16]. Among the above carriers, porous MOF is a new class of material that shows excellent capa- bility as a drug carrier material because of their tunable pore size, high surface area, and well-ordered arrangement of metal http://dx.doi.org/10.1016/j.colsurfb.2017.09.011 0927-7765/© 2017 Published by Elsevier B.V.