Recent advances on fluorescent biomarkers of near-infrared quantum dots for in vitro and in vivo imaging

Abstract

Luminescence probe has been broadly used for bio-imaging applications. Among them, near-infrared (NIR) quantum dots (QDs) are more attractive due to minimal tissue absorbance and larger penetration depth. Above said reasons allowed whole animal imaging without slice scan or dissection. This review describes in vitro and in vivo imaging of NIR QDs in the regions of 650-900 nm (NIR-I) and 1000-1450 nm (NIR-II). Also, we summarize the recent progress in bio-imaging and discuss the future trends of NIR QDs including group II-VI, IV-VI, I-VI, I-III-VI, III-V, and IV semiconductors.

Keywords: 204 Optics / Optical applications; 60 New topics / Others: Nanocrystals, Quantum dots, Bioimaging, Biomarkers, Fluorescence imaging; NIR imaging; Quantum dots; bio-marker; review.

Graphical abstract

Figure 1.

(a) Human skin absorption spectra in the of NIR-I, NIR-II, and NIR-III regions. (b) Absorption and scattering spectra from oxygenated blood, deoxygenated blood, skin and fatty tissue. Reproduced with permission from (Figure 1(a), [14] Copyright 2009 RSC Publishing; Figure 1(b), [18] Copyright 2016 RSC Publishing).

Figure 2.

(a) PL emission spectra of CdTe_0.15 Se_0.85 QDs under different growth times. (b) NIR QDs with emission tunable from 700–800 nm (excitation = 450 nm). (c) Absorbance (blue) and emission (black) of HgTe QDs suspended in TCE. (d) Dual-color immunofluorescence cellular imaging (scale bar: 20 mm). The Hela cells are labeled by the QDs/protein conjugates (red) and Hoechst (blue). (e) Multiplex imaging capability of CdTe/CdSe QDs in live animals. f) CdTe QDs under UV irradiation (λ_ex = 365 nm). Reproduced with permission from (Figure 2(a), [21] Copyright 2014 Wiley Publishing; Figure 2(b), [22] Copyright 2011 Wiley Publishing; Figure 2(c), [23] Copyright 2018 Nature Publishing Group; Figure 2(d), [22] Copyright 2011 Wiley Publishing; Figure 2(e), [29] Copyright 2011 RSC Publishing; and Figure 2(f), [22] Copyright 2011 Wiley Publishing).

Figure 3.

(a) PL spectra of the PbS QDs synthesized by the droplet-based capillary reactor. (b) Comparison of relative PL spectra for IR-26 and a 0.98 eV PbSe QD. (c) The spectral range of different PbS/CdS/ZnS QDs. (d) The nude mice injected with AuNCs-PbS-QDs, AuNCs-PbS-QDs/AA, and AuNCs-PbS-QDs/AA/AOase, respectively. All the images were taken under two filters of DsRed and ICG. (e) Whole body and corresponding intensity surface, and ex vivo NIR fluorescence images of the liver (left inset) and spleen (right inset) of a mouse 24 h after tail vein injection of LNH₂ capped QDs. Reproduced with permission from (Figure 3(a), [33] Copyright 2014 The American Chemical Society; Figure 3(b), [32] Copyright 2010 The American Chemical Society; Figure 3(c), [39] Copyright 2015 Wiley Publishing; Figure 3(d), [38] Copyright 2015 The American Chemical Society; and Figure 3(e), [45] Copyright 2018 RSC Publishing).

Figure 4.

(a) PL spectra of Ag₂Se QDs with different reaction times (b) PL spectra of monodispersed Ag₂Se QDs with different sizes (molar ratio of Ag: Se = 6:1, 5:1, and 4:1). (c) Emission spectra of Ag₂Se QDs capped with a multidentate polymer (samples S1−S5 corresponding to 0.5, 1, 1.5, 2, and 3 h reaction). (d) Overlay image (confocal laser scanning microscopy and NIR) of the Cu-2-{2-chloro-6-hydroxy-5-[(2-methyl-quinolin-8-ylamino)-methyl]-3-oxo-3H-xanthen-9-yl}-benzoic acid (CuFl) stained cells after incubation with the Ag₂S-GSH-SNO NPs for 3 h. (e) In vivo imaging of PEGylated Ag₂Se QDs in mice after intravenous injection. (Top row) Abdomen imaging; (bottom row) backside imaging. Reproduced with permission from (Figure 4(a), [52] Copyright 2013 The American Chemical Society; Figure 4(b), [60] Copyright 2012 The American Chemical Society; Figure 4(c), [54] Copyright 2014 The American Chemical Society; Figure 4(d), [53] Copyright 2013 The American Chemical Society; and Figure 4(e), [ 48] Copyright 2016 The American Chemical Society).

Figure 5.

(a) The PL spectra of CuInS₂ QDs at different reaction times. (b) PL spectra of RNase A-CuInS₂ QDs at different reaction temperatures. (c) PL spectra of AgInS₂/ZnS NCs by heating the Ag/In/Zn/S (1:1:0.5:2.5) solution from 90 to 180 °C. (d) Vis–NIR absorption and PL spectra of AgInS₂QDs capped with a multidentate polymer synthesized for 105 min; (inset) bright-field image and PL image in pseudocolor. (e) PL spectra of AgInSe₂ QDs prepared with different Ag: In molar ratios. The inset shows AgInSe₂ QDs (Ag: In molar ratio of 2:1) in water, excited with a UV lamp at 365 nm. (f) Mice after treatment with the RNase A-CuInS₂ QDs. Reproduced with permission from (Figure 5(a), [80] Copyright 2016 RSC Publishing; Figure 5(b), [74] Copyright 2017 RSC Publishing; Figure 5(c), [73] Copyright 2014 The American Chemical Society; Figure 5(d), [76] Copyright 2015 Elsevier publishing; Figure 5(e), [78] Copyright 2016 Elsevier publishing; and Figure 5(f), [74] Copyright 2017 RSC Publishing).

Figure 6.

(a) PL spectra of InP QDs grown at 250 °C for 4 h before (black line) and after (red line) HF etching. Photographs of both colloidal solutions under UV illumination (inset top-366 nm) and UV/white light flash (inset bottom). (b) PL spectra of differently sized InP QDs and Cu: InP d-dots (c) PL of InAs (Zn_0.7Cd_0.3S) during shell growth from 0–2.5 monolayers. (d) In vivo, NIR fluorescence imaging of 22B tumor-bearing mice (arrows) injected with QD800-MPA and QD800-COOH, respectively. Reproduced with permission from (Figure 6(a), [83] Copyright 2008 Wiley Publishing; Figure 6(b), [81] Copyright 2014 The American Chemical Society; Figure 6(c), [82] Copyright 2010 The American Chemical Society; and Figure 6(d), [ 85] Copyright 2010 Wiley Publishing).

Figure 7.

(a) PL spectra of tetrachloroethylene solutions of Ge-NC (100/0), Ge-NC (0/100), and Ge-NC (50/50) under 405 nm excitation. PL QY values are shown in percentage. (b) Normalized PL spectra of NCSi-OD/F127-COOH, HiLyte Fluor 750 amine dye and NCSi-OD/F127-COOH conjugated with the dye when excited at 350 nm. (c) PL spectra of a colloidal solution of codoped Si QDs. The growth temperatures are 1050 (solid) and 1200 °C (dashed). (d) Fluorescence spectra obtained for multiphoton excitation associated with incident intensities at; 1200 nm excitation (inset: excitation at 1200 nm and 22 mW). (e) SWIR fluorescence images of FCDs in aqueous dispersions, excited by lasers and captured with an InGaAs camera. Images in the bottom row are the heat maps of those in the upper row. Reproduced with permission from (Figure 7(a), [104] Copyright 2010 The American Chemical Society; Figure 7(b), [107] Copyright 2016 RSC Publishing; Figure 7(c), [141] Copyright 2016 RSC Publishing; Figure 7(d), [97] Copyright 2018 RSC Publishing; and Figure 7(e), [96] Copyright 2018 RSC Publishing).

Figure 8.

a). Schematic illustration of SLN mapping using a nanoscale imaging probe. Imaging probes on the 5–10 nm size scale can flow through the SLN into adjacent nodes in the chain; nanoprobes >300 nm in size rarely leave the injection site. Nanoprobes with a hydrodynamic diameter of 10–50 nm exhibit rapid uptake into SLN and do not leave. b). NIR QD sentinel lymph node mapping in the mouse; Images of mouse injected intradermally with 10 pmol of NIR QDs in the left paw. Left, pre-injection NIR autofluorescence image; middle, 5 min post-injection white light color video image; right, 5 min post-injection NIR fluorescence image. An arrow indicates the putative axillary sentinel lymph node. Fluorescence images have identical exposure times and normalization. c). Sentinel lymph node imaging following localization of Si QDs in an axillary position. Autofluorescence is coded in green, and the unmixed Si QD signal is coded in red. Reproduced with permission from (Figure 8(a), [143] Copyright 2012 The American Chemical Society; Figure 8(b), [145] Copyright 2004 Nature Publishing Group; and Figure 8(c), [150] Copyright 2011 The American Chemical Society).