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Biodegradable and Magnetic-Fluorescent Porous Silicon@Iron Oxide Nanocomposites for Fluorescence/ Magnetic Resonance Bimodal Imaging of Tumor in Vivo Bing Xia, Jiachen Li, Jisen Shi, Yu Zhang, Qi Zhang, Zhenyu Chen, and Bin Wang ACS Biomater. Sci. Eng., Just Accepted Manuscript • DOI: 10.1021/acsbiomaterials.7b00467 • Publication Date (Web): 22 Aug 2017 Downloaded from http://pubs.acs.org on August 24, 2017
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ACS Biomaterials Science & Engineering
Biodegradable and Magnetic-Fluorescent Porous Silicon@Iron Oxide Nanocomposites for Fluorescence/Magnetic Resonance Bimodal Imaging of Tumor in Vivo
Bing Xia,*,†,‡ Jiachen Li,‡ Jisen Shi,† Yu Zhang,§ Qi Zhang,‡ Zhenyu Chen,† and Bin Wang ‡
†
Key Laboratory of Forest Genetics & Biotechnology (Ministry of Education of
China), Nanjing Forestry University, Nanjing 210037, P. R. China ‡
Advanced Analysis & Testing Center, College of Science, Nanjing Forestry
University, Nanjing 210037, P. R. China §
State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials
and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center for Suzhou Nano Science and Technology, Southeast University, Nanjing 210096, P. R. China
Corresponding
authors
*E-mail:
[email protected],
ORCID
iDs:
0000-0002-1637-7908
KEYWORDS: magnetic-fluorescent nanocomposites, porous silicon, iron oxide nanoparticles, multimodal imaging, in vivo
ABSTRACT: Considering future clinical transaction, biodegradable and luminescent porous silicon nanoparticles instead of traditional heavy-metal quantum dots have an
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important significance on the construction of biodegradable and magnetic-fluorescent nanocomposites.
Herein,
to
fabricate
PSiNPs@Fe3O4
nanocomposites,
super-paramagnetic iron oxide nanoparticles were covalently incorporated into luminescent porous silicon nanoparticles by microwave-induced hydrosilylation. These resultant nanocomposites had near-infrared fluorescence (500 nm – 800 nm), and super-paramagnetism with high magnetic saturation value of 141 emu/g. The aqueous-dispersibility of PSiNPs@Fe3O4 nanocomposites could be significantly improved via simple ultrasonication in water. Furthermore, they also exhibited an excellent biodegradability and biocompatibility, whether in vitro or in vivo. Finally, their ability of fluorescence/magnetic resonance bimodal imaging had been successfully demonstrated for cancer cells in vitro or tumor tissues in vivo, respectively.
1. INTRODUCTION Magnetic-fluorescent nanocomposites assembled by super-paramagnetic iron oxide (Fe3O4 or Fe2O3) nanoparticles (SPIONs) and fluorescent quantum dots (QDs) have exhibited wide potential applications on early diagnosis and timely therapy of cancer (e.g., cancer-related biomarker enrichment and monitoring, cancerous cell separation and analysis, fluorescence or magnetic resonance imaging (MRI), magnetic-targeted drug delivery, magnetic hyperthermia therapy, imaging-guided combination therapy, etc.).1-5 Particularly, magnetic-fluorescent nanocomposites can be greatly helpful to monitor the occurrence and development of cancers in body, and significantly improve the early diagnosis outcomes, due to their multimodal imaging ability combining fluorescence imaging with high sensitivity and MRI with high resolution.6-10 Yet despite successful human uses of biodegradable and non-toxic iron
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ACS Biomaterials Science & Engineering
oxide nanoparticles approved by US Food and Drug Administration (FDA),11-14 the toxicity concern associated with heavy-metal QDs contained in magnetic-fluorescent nanocomposites limits their further clinical transactions, due to the leakage of the inherent toxic elements (Hg, Cd, Se, Te, In, As, and Pb) and non-degradation in body.15-18 As a promising alternative to heavy-metal QDs, intrinsic luminescent porous silicon nanoparticles (PSiNPs) have competitive advantages in biomedical imaging, because of their tunable fluorescence from blue to near infrared (NIR) emission, and controlled porous nanostructures with a high loading capability of various contrast agents.19-25 Compared to heavy-metal-based QDs, PSiNPs consisting of silicon element is expected to be non-toxic. Especially, they can be ultimately degraded into orthosilicic acid (Si(OH)4), and then excreted through the urine in body.26-28 Considering future clinical transaction, the construction of biodegradable and magnetic-fluorescent nanocomposites based on PSiNPs has important significance on the development of multimodal imaging in vivo. It was reported that luminescent PSiNPs as host matrix were physically incorporated with SPIONs, which were simultaneously endowed with an excellent magnetism and fluorescence.29,30 However, no relative multimodal imaging in vivo was further demonstrated. Herein, to fabricate stable PSiNPs@Fe3O4 nanocomposites for in vivo applications, Fe3O4 nanoparticles containing terminal C=C bonds were synthesized, and then anchored into hydrogen-terminated PSiNPs by microwave-induced hydrosilylation (shown in Figure 1). And then, their fluorescence, magnetism, biocompatibility, and biodegradability were systematically characterized and evaluated. Finally, their ability of fluorescence/magnetic resonance bimodal imaging was demonstrated for cancer cells in vitro or tumor tissues in vivo, respectively.
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2. EXPERIMENTAL SECTION 2.1. Materials and Instruments. The single side polished, (100) oriented, and p-type silicon wafers (boron doped, 8~10 Ω cm resistivity) were purchased from Hefei Kejing Materials Technology Co. Ltd., China. 10-undecenoic acid was purchased from Sigma-Aldrich Chemicals, USA. Others chemicals were bought from Sinopharm Chemical Reagent, China. Deionized (DI) water (≥18 MΩ cm resistivity, Millipore) was used as solvent for preparing various aqueous solutions. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium
bromide
(MTT)
and
DMEM culture medium were all obtained from KenGEN Biotechnology Co. Ltd., China. UV-vis-NIR adsorption spectra were recorded by a Lambda 950 spectrophotometer. Photoluminescence (PL) spectra and time-resolved PL spectra were performed using a Perkin-Elmer LS55 and FluoroLog-3 fluorescence spectrometer, respectively. The chemical composition and functional groups of smaples were also detected using transmission Fourier transform infrared spectroscopy (FTIR) (Vertex 80, Bruker, USA). The crystal parameter of samples was analyzed with X-ray diffraction (XRD) (Ultimal IV, Rigaku, Japan). X-ray photoelectron spectra (XPS) were recorded by Kratos AXIS Ultra DLD system with a monochromatic Al Kα X-ray beam (1486.6 eV) at 150 W in a residual vacuum of
