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WIREs Nanomed Nanobiotechnol
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Recent advances in applications of nanoparticles in SERS in vivo imaging

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Abstract Surface‐enhanced Raman scattering (SERS) technique has been regarded as one of the most important research methods in the field of single‐molecule science. Since the previous decade, the application of nanoparticles for in vivo SERS imaging becomes the focus of research. To enhance the performance of SERS imaging, researchers have developed several SERS nanotags such as gold nanostars, copper‐based nanomaterials, semiconducting quantum dots, and so on. The development of Raman equipment is also necessary owing to the current limitations. This review describes the recent advances of SERS nanoparticles and their applications for in vivo imaging in detail. Specific examples highlighting the in vivo cancer imaging and treatment application of SERS nanoparticles. A perspective on the challenges and opportunities of nanoparticles in SERS in vivo imaging is also provided. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Schematic illustration of SERS‐based direct detection and indirect detection. (Reprinted with permission from B. Ren et al., Copyright 2015 John Wiley and Sons)
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(a) Following stimulation, CAEC express adhesion molecules detectable via immuno‐SERS imaging in multiplex formats, and the representative spectra from anti‐ICAM‐1 (purple), anti‐VCAM‐1 (red) and anti‐P‐selectin (blue) BFNP. (b) SERS spectroscopy was conducted on atherosclerotic (red lines) and nonatherosclerotic (black lines) regions of the intact artery. (c) SERS mapping of anti‐ICAM‐1 (purple), anti‐VCAM‐1 (red), anti‐P‐selectin (blue), and isotype (green) BFNPs in nonatherosclerotic (up) and atherosclerotic (down) artery. Scale bars: 500 μm (black bar) and 20 μm (white bar). (d) To conduct SERS‐BFNP molecular imaging. (e) SERS spectra acquired from mice that received a mixture of BFNPs. (Reprinted with permission from P. Maffia et al., Copyright 2018 Ivyspring International Publisher). CAEC, coronary artery endothelial cells; ICAM‐1, intercellular adhesion molecule 1; VCAM‐1, vascular cell adhesion molecule 1; BFNPs, antibody‐functionalized gold nanoprobes
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(a) Illustration of gold nanostars for intracellular and in vivo SERS detection and real‐time drug delivery using plasmonic‐tunable Raman/FTIR imaging. This system can directly track the delivery and release of MTX from gold nanostars in single living cells and in mice in real‐time manner. (Reprinted with permission from D. Cui et al., Copyright 2016 Elsevier). MTX, mitoxantrone
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(a) Schematic illustration of the intraoperative precise SERS imaging and the thermal ablation of residual microtumors in the orthotopic prostate metastasis tumor model. (b) Temperature change curves of GERTs solution and water with an 808 nm laser irradiation. (c) The experimental process of intraoperative Raman imaging‐guided photothermal ablation of residual microtumors. (d) The digital photograph and Raman imaging of tumors before or after surgical resection. Raman image clearly shows multiple residual microtumors on the resection bed (Arrow 1) or metastasized to the bladder (Arrow 2). Arrow 3 indicates the signal from normal bladder tissue. GERTs‐positive foci are confirmed to be microscopic tumor cell deposits by H&E staining. (Reprinted with permission from Z. Xiao et al., Copyright 2018 American Chemical Society). GERTs, gap‐enhanced Raman tags
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(a) Illustration of the SERS NP. (b) TEM imaging of the SERS NPs. (c) SERS spectrum of the NPs depends on the Raman reporter molecule (trans −1,2‐bis(4 pyridyl)ethylene (BPE)). (d) SERS NPs enable delineation of liver tumors and microscopic liver tumors by MRI and SERS imaging. (e) Comparison of SERS NPs versus ICG as contrast agents in vivo. The two contrast agents have similar performance when demarcating the tumors. However, the ICG exhibits a false positive area indicated by the arrowhead. (Reprinted with permission from M. Kircher et al., Copyright 2016 American Chemical Society). TEM, transmission electron microscopy; ICG, indocyanine green
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(a) Synthesis of UCF‐SERS dots and their UCF and SERS dual mode imaging. (b) TEM image of [email protected]2@Ag nanocomposites. (c) Normal and fluorescence images of UCF‐SERS dots solution (0.65 mg ml−1). (d) Fluorescence images of the different thickness pork tissue slices blocked UCF‐SERS Dots solution. (e) UCF and SERS spectra of the UCF‐SERS dots subcutaneously injected Kunming rat under 980 nm (0.5 W/cm2) and 785 nm ((200 mW) laser excitation, respectively. (Reprinted with permission from L. Chen et al., Copyright 2014 American Chemical Society). UCF, upconversion fluorescence; UCNP, upconversion nanoparticles
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(a) Schematic of the endoscopic imaging of a rat esophageal tumor model. (b) Photograph of a surgically exposed rat esophagus implanted with three tumor xenografts. (c) Raman spectrum of the SERS NPs that were mixed together. (d) Raman spectrum of a variety of backgrounds. (e) Images showing the concentration ratio of EGFR‐NPs versus isotype‐NPs and HER2‐NPs versus isotype‐NPs. (Reprinted with permission from J. Liu et al., Copyright 2015 Optical Society of America)
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(a) Typical TEM images of Au nanostars, synthesized via addition of 135 μl of Au seed (main image, Scale bar is 50 nm) and 45 μl of Au seed (inset, Scale bar is 100 nm). (Reprinted with permission from T. Vo‐Dinh et al., Copyright 2008 American Chemical Society). (b) The porous Au–Ag alloy NPs and their SERS activities. (Reprinted with permission from C. Gao et al., Copyright 2016 American Chemical Society). (c) Schematic diagram and TEM image of gap‐enhanced Raman tags. Scale bar is 50 nm. (Reprinted with permission from Z. Xiao et al., Copyright 2018 American Chemical Society). Au–Ag alloy NPs, gold−silver alloy nanoparticles
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The structure of a SERS nanotag, consisting of a SERS‐active nanoparticle core, adsorbed Raman probe molecules on the surface, and a biocompatible layer
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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