In Vivo Fluorescence Imaging in the Second Near-Infrared Window with Long Circulating Carbon Nanotubes Capable of Ultrahigh Tumor Uptake

Abstract

Cancer imaging requires selective high accumulation of contrast agents in the tumor region and correspondingly low uptake in healthy tissues. Here, by making use of a novel synthetic polymer to solubilize single-walled carbon nanotubes (SWNTs), we prepared a well-functionalized SWNT formulation with long blood circulation (half life ~ 30 h) in vivo to achieve ultra-high accumulation of ~30% injected dose (ID)/gram in 4T1 murine breast tumors in Balb/c mice. Functionalization dependent blood circulation and tumor uptake was investigated through comparisons with phospholipid-PEG solubilized SWNTs. For the first time, we performed video-rate imaging of tumors based on the intrinsic fluorescence of SWNTs in the second near infrared (NIR-II, 1.1–1.4 µm) window. We carried out dynamic contrast imaging through principal component analysis (PCA) to immediately pinpoint the tumor within ~20 s post injection. Imaging over time revealed increasing tumor contrast up to 72 h post injection, allowing for its unambiguous identification. 3D reconstruction of the SWNTs distribution based on their stable photoluminescence inside the tumor revealed a high degree of colocalization of SWNTs and blood vessels, suggesting enhanced permeability and retention (EPR) effect as the main cause of high passive tumor uptake of the nanotubes.

Neodymium-doped nanoparticles for infrared fluorescence bioimaging: The role of the host

“…27 Although the number of infrared-emitting fluorescent nanoprobes working in the BWs is reduced compared to that of visible-emitting NPs, different IR-emitting QDs, C-NPs, and RENPs have been synthesized and studied for deep tissue in vivo imaging purposes. [28][29][30] Among all these IR-emitting systems, neodymium-doped NPs (Nd:NPs) arise as exceptional candidates for in vivo fluorescence imaging due to their unique combination of properties. First of all, Nd:NPs can be optically excited with 808 nm laser radiation, which is a nonheating, non-damaging wavelength that can be provided by a commercially available and cost-effective laser diode.…”

LaF3 core/shell nanoparticles for subcutaneous heating and thermal sensing in the second biological-window

“…17 In particular, the applicability in the second biological window (II-BW) opens up the possibility of not only deep tissue imaging but also of high contrast, autofluorescence free in vivo fluorescence thermal sensing, as it has already been demonstrated in imaging applications. [18][19][20][21][22][23][24][25] As an additional requirement, the multifunctional NPs to be used should operate under infrared radiation single beam excitation at wavelength avoiding any non-selective cellular damage. Recent studies dealing with the heating effects and the light-induced cytotoxicity during in vitro imaging experiments have pointed out 808 nm as an optimal excitation wavelength, since it simultaneously minimizes both the laser-induced thermal loading of the tissue and the intracellular photochemical damage.…”

Graphene-Based Nanomaterials in Bioimaging

“…were covalently linked to GO/rGO for FL imaging and active targeting, respectively. Meanwhile, this approach was also employed for radionuclide labeling, such as 125 I (44), 64 Cu (54), 66 Ga (56), 198,199 Au (57), 111 In (58), and so on. The radionuclide-labeled GOs can be used for PET/SPECT imaging.…”

“…However, this modality suffers from poor tissue penetration (0-2 cm), strong tissue scattering of photons in the visible light region (395-600 nm) (62), and significant background because of tissue autofluorescence and light absorption by proteins (257-280 nm), heme groups (absorbance maximum at 560 nm), and even water (above 900 nm) (63). To address these issues, nearinfrared window (NIR, 650-900 nm) (64) and second NIR window (NIR-II, 1000-1700 nm) (65,66) imaging modalities have been explored with the advantages of reduced autofluorescence, reduced tissue scattering, and greater depth of penetration for in vivo imaging.…”