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Protein-Stabilized Gadolinium Oxide-Gold Nanoclusters Hybrid for Multimodal Imaging and Drug Delivery Lu Han, Jun-Mei Xia, Xin Hai, Yang Shu, Xu-Wei Chen, and Jian-Hua Wang ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.7b00246 • Publication Date (Web): 08 Feb 2017 Downloaded from http://pubs.acs.org on February 8, 2017
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ACS Applied Materials & Interfaces
Protein-Stabilized Gadolinium Oxide-Gold Nanoclusters Hybrid for Multimodal Imaging and Drug Delivery Lu Han1, Jun-Mei Xia1, Xin Hai1, Yang Shu1,2*, Xu-Wei Chen1 and Jian-Hua Wang1* 1
Research Center for Analytical Sciences, Department of Chemistry, College of
Sciences, Northeastern University, Box 332, Shenyang 110189, China 2
Institute of Biotechnology, College of Life and Health Sciences, Northeastern
University, Box H006, Shenyang 110189, China
Keywords: gadolinium oxide; gold nanocluster, near-infrared fluorescence; magnetic resonance imaging; X-ray computed tomography; photothermal/photodynamic therapy. Abstract: A protein-stabilized multifunctional theranostic nanoplatform, gadolinium oxide-gold nanoclusters hybrid (Gd2O3-AuNCs), is constructed for multimodal imaging and drug delivery. The Gd2O3-AuNCs nanohybrid is developed by integrating Gd2O3 nanocrystals and gold nanoclusters into bovine serum albumin scaffold as a stabilizer. The nanohybrid exhibits favorable biocompatibility and is capable of enhancing the contrast in magnetic resonance (MR) and X-ray computed tomography (CT) imaging. Meanwhile, the integrated AuNCs component not only endows the nanohybrid to produce red fluorescence, but also sensitizes the generation of singlet oxygen (1O2) upon near-infrared laser stimulation at 808 nm. Bovine serum albumin surrounding the nanoparticles makes Gd2O3-AuNCs a brilliant carrier for the delivery of indocyanine green (ICG). ICG loading endows the Gd2O3-AuNCs-ICG 1
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nanocomposite with a near-infrared fluorescence imaging capability, and improves its photodynamic property and photothermal capability. Ultimately, further experiments have demonstrated that Gd2O3-AuNCs-ICG nanocomposite is a promising theranostic agent for image guided cancer therapy.
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ACS Applied Materials & Interfaces
INTRODUCTION In the past decade, various theranostic nanoplatforms have been exploited for simultaneous tumor diagnosis and therapy.1-7 A number of imaging techniques, e.g., near-infrared fluorescence (NIRF)8, photoacoustics9, ultrasound10, magnetic resonance (MR)11, X-ray computed tomography (CT)12 and position emission tomography (PET)13 are introduced to these platforms for tumor diagnosis, with therapeutic methods of chemo14, photothermal (PTT)15 and photodynamic (PDT)16 therapy. Among the diverse diagnostic techniques, MR imaging is a powerful noninvasive modality with high spatial resolution. Gadolinium(III) is known as an excellent contrast agent for MR imaging, and commercial Gd(III)-chelate is extensively employed in clinics.17 A variety of nanostructures functionalized with Gd(III)-chelate were constructed for imaging-guided cancer treatment.18-20 Gadolinium(III)-chelated silica nanospheres have been demonstrated to be useful vehicle to deliver doxorubicin and indocyanine green for performing simultaneous cancer diagnosis and chemo-photothermal therapy.21 Further, gadolinium oxide nanocrystals were proven to exhibit a larger proton relaxivity with respect to Gd-chelates22,23, which makes them a promising material to develop new theranostic platforms.24 Moreover, theraputic agents based on gold nanostructures have recently attracted extensive attentions.25,26 Various gold nanoparticles with tunable size and morphology, e.g., nanoshells27, nanorods28 and nanocages29, have been reported for biosensing, bioimaging, drug delivery and photothermal therapy. Apart from favorable biocompatibility and unique optical property, the above mentioned gold
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nanostructures possess high X-ray attenuation coefficient and are prevailing as CT contrast agents.2,30 In particular, small sized gold nanoparticles of
