A route to brightly fluorescent carbon nanotubes for near-infrared imaging in mice

Abstract

The near-infrared photoluminescence intrinsic to semiconducting single-walled carbon nanotubes is ideal for biological imaging owing to the low autofluorescence and deep tissue penetration in the near-infrared region beyond 1 µm. However, biocompatible single-walled carbon nanotubes with high quantum yield have been elusive. Here, we show that sonicating single-walled carbon nanotubes with sodium cholate, followed by surfactant exchange to form phospholipidpolyethylene glycol coated nanotubes, produces in vivo imaging agents that are both bright and biocompatible. The exchange procedure is better than directly sonicating the tubes with the phospholipid-polyethylene glycol, because it results in less damage to the nanotubes and improves the quantum yield. We show whole-animal in vivo imaging using an InGaAs camera in the 1-1.7 µm spectral range by detecting the intrinsic near-infrared photoluminescence of the 'exchange' single-walled carbon nanotubes at a low dose (17 mg l −1 injected dose). The deep tissue penetration and low autofluorescence background allowed high-resolution intravital microscopy imaging of tumour vessels beneath thick skin.Single-walled carbon nanotubes (SWNTs) have shown potential for biological and medical 1 applications because of their intrinsic optical properties and ability to load both targeting ligands and chemotherapy drugs, in vitro 2,3 and in vivo 4-6. Their unique optical properties make SWNTs attractive candidates for biological imaging7 -11 and sensing12. In particular, the near-infrared (NIR) photoluminescence of semiconducting SWNTs13 has made them promising as NIR fluorescent contrast agents in biological systems8 -11. SWNT NIR fluorescent probes with emission mostly in the infrared-A (IR-A, 1-1.4 µm) region (Fig. 1) are ideal as biological probes because of the inherently low autofluorescence in the NIR range (0.8-1.7 µm) 14 and large Stokes shift between the excitation and emission bands, which allows excitation in the biological transparency window15 near 800 nm while further reducing the background effects of autofluorescence and scattering. Work carried out by Lim and colleagues16 has predicted that NIR fluorophores with emission in the 1,100-1,400 nm range have higher tissue penetration than those near 800 nm by considering the

Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window

“…This benefit is further enhanced by a large Stokes shift between emission and excitation resonances [≥300 nm; see Fig. S10 for photoluminescence excitation/emission (PLE) spectrum], leading to further suppression of endogenous autofluorescence (18,34). One issue is that the relatively low quantum yield (QY) of SWNTs may limit its future applications.…”

“…The preparation of brightly fluorescent exchanged-SWNTs with high biocompatibility can be found in detail in ref. 18 by using a surfactant exchange method to minimize damage to SWNTs. A fluorescence emission spectrum of the resulting SWNTs with DSPE-mPEG coating at 808-nm excitation is shown in Fig.…”

“…QDs (11) such as PbSe (12), PbS (13), and CdHgTe (14) are promising candidates for imaging in the NIR II; however, in vivo animal imaging in the NIR II region with QDs has not been carried out thus far. As an alternative, singlewalled carbon nanotubes (SWNTs) have shown promise as fluorescent imaging agents in the NIR II both in vitro and in vivo (15)(16)(17)(18). In this work, we apply bright, biocompatible SWNTs as NIR II fluorophores for video-rate in vivo imaging.…”

Room-temperature near-infrared silicon carbide nanocrystalline emitters based on optically aligned spin defects

“…A natural strategy to fulfil the property (i) is to use group-IV (carbon and silicon) nanomaterials. Indeed, carbon nanotubes (from 1.8 µm down to 50 nm in length) have been applied for deep-tissue imaging 15,16 because of their NIR PL in the spectral range from 900 nm to 1500 nm.…”

Over-1000 nm near-infrared fluorescent biodegradable polymer nanoparticles for deep tissue in vivo imaging in the second biological window

“…The OTN-NIR region consists of the 'NIR-II' (the second biological window: 1000-1350 nm) and the 'NIR-III' (the third biological window: 1500-1800 nm) regions, and NIR light in these regions can penetrate the body deeper than the currently used NIR-I (first biological window: 700-900 nm) region. [3][4][5] Various nanomaterials, such as quantum dots, 6 single-wall carbon nanotubes 7 and rareearth-doped ceramic nanoparticles, [8][9][10][11] are well known to demonstrate OTN-NIR emission; many researchers, including our group, have reported successful in vivo fluorescence imaging using these nanomaterials. However, synthesis of these nanoparticles requires high levels of chemical experimental skill and is time consuming.…”