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Plasmonic Nanoprobe of (Gold Triangular Nanoprism Core)/(Polyaniline Shell) for Real-time Three-dimensional pH Imaging of Anterior Chamber Peijun Tang, Xueqin Jiang, Yangyang Wang, Huanjun Chen, Yu Shrike Zhang, Panpan Gao, Hao Wang, Xuemeng Li, and Jianhua Zhou Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.7b01623 • Publication Date (Web): 15 Aug 2017 Downloaded from http://pubs.acs.org on August 17, 2017
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Analytical Chemistry
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Plasmonic Nanoprobe of (Gold Triangular Nanoprism
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Core)/(Polyaniline Shell) for Real-time Three-dimensional
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pH Imaging of Anterior Chamber
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Peijun Tang1 , Xueqin Jiang1 , Yangyang Wang1, Huanjun Chen2, Yu Shrike Zhang 3,
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Panpan Gao1, Hao Wang2, Xuemeng Li1, and Jianhua Zhou1*
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§
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1
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Province, Department of Biomedical Engineering, School of Engineering, Sun
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Yat-sen University, Guangzhou 510275, China
Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong
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2
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Key Laboratory of Display Material and Technology, School of Electronics and
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Information Technology, Sun Yat-sen University, Guangzhou 510275, China
State Key Lab of Optoelectronic Materials and Technologies, Guangdong Province
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3
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Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA
Division of Engineering in Medicine, Department of Medicine, Brigham and
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*Corresponding author:
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Tel.: +86 20 39387890; Fax: +86 20 39387890.
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E-mail:
[email protected] (J. H. Zhou)
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§Tang, P. J. and Jiang, X. Q. contributed equally and are co-first authors. 1
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Analytical Chemistry
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Abstract:
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Three-dimensional (3D) molecular imaging enables the study of biological processes
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in both living and nonviable systems at the molecular level and has a high potential on
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early diagnosis. In conjunction with specific molecular probes, optical coherent
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tomography (OCT) is a promising imaging modality to provide 3D molecular features
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at
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(gold-triangular-nanoprism-core)/(polyaniline-shell nanoparticles) (GTNPs@PANI)
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as an OCT contrast agent and pH-responsive nanoprobe for 3D imaging of pH
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distribution. These core/shell nanoparticles possessed significantly different extinction
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and scattering properties in acid and basic microenvironments. The switch of the
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optical features of the nanoparticles upon pH change was reversible and the response
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time was less than 1.0 s. The nanoprobe successfully indicated the acid regions of a
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mimic tumor from the basic region in a gelatin-based phantom under OCT imaging.
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As a demonstration of practical applications, real-time 3D OCT imaging of pH and
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lactic acid in the anterior chamber of a fish eye was realized by GTNPs@PANI
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nanoparticles. Using GTNPs@PANI nanoparticles as the contrast probes for OCT
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imaging, non-invasive, and real-time molecular imaging in both living and nonviable
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systems at microscale can be achieved.
the
tissue
level.
In
this
study,
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introduced
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Analytical Chemistry
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Three-dimensional (3D) molecular imaging can advance the understanding of
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biological processes in both living and nonviable systems at the molecular level and
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contribute to early diagnosis, such as early detection of cancer or ocular inflammation.
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It therefore has become an important direction in the field of bioimaging and medical
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imaging.1-11 Among all of the molecules in the human body, hydrogen ion (whose
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concentration is usually described by pH) is important in the clinic because alterations
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in tissue pH underlie many basic metabolic processes and pathological processes,
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including inflammation, renal diseases, and chronic lung disorders.12-14 In tumors,
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extracellular pH is lower compared to normal tissues, which is due to increased lactic
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acid production, reduced interstitial fluid buffering, and reduced perfusion.14,15 In
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aqueous humor, hypoxia caused by wearing contact lenses,16 metabolism of glucose
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by the ciliary epithelium and retina,17 and prolonged contraction of ciliary, are
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believed to result in an increase in the amount of lactic acid. This leads to the
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reduction of pH in aqueous humor, compared to its normal pH values in the range of
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7.4~7.5. Hence, 3D imaging of the spatial distribution of pH can contribute to our
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understanding of early diagnosis and offer new ways of detecting diseases, such as
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tumors, diabetic eye diseases, and asthenopia.
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For the imaging of pH in humans, there are three major clinical modalities,
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including magnetic resonance imaging (MRI), positron emission tomography (PET),
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and fluorescence microscopy imaging (FMI).18-21 Major targets of the pH imaging
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measured by these imaging technologies can be divided in two types according to
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their sizes. One is associated with MRI and PET, which are objects in
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centimeter-scales, such as tumors,22,23 large organs (e.g. renal),24 limbs (e.g. human
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calf muscles),25 among others. The other type is tissues at cellular-scales imaged by
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the FMI.26-29 However, for 3D imaging of pH of body fluid in relatively small organs
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(e.g. eye, skin, and superficial vessel) or microtumors, these three modalities then
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become unsuitable. MRI is limited by its low sensitivity in depicting molecular 3
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contrast agents as well as relatively low resolution (~1 mm).30,31 PET is accompanied
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by radioactive damages and low spatial resolution (3-7 mm).32,33 FMI possesses high
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sensitivity and resolution,20,34 but it suffers from confined millimeter-scale imaging
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region, background autofluorescence, and shallow penetration depth (
