Fluorescent Nanoprobes Dedicated to in Vivo Imaging: From Preclinical Validations to Clinical Translation

Département MicroTechnologies Pour la Biologie et la Santé CEA-LETI, Minatec, 17 Rue des Martyrs, 38045 Grenoble Cedex, France.
Molecules (Impact Factor: 2.42). 12/2012; 17(5):5564-91. DOI: 10.3390/molecules17055564
Source: PubMed


With the fast development, in the last ten years, of a large choice of set-ups dedicated to routine in vivo measurements in rodents, fluorescence imaging techniques are becoming essential tools in preclinical studies. Human clinical uses for diagnostic and image-guided surgery are also emerging. In comparison to low-molecular weight organic dyes, the use of fluorescent nanoprobes can improve both the signal sensitivity (better in vivo optical properties) and the fluorescence biodistribution (passive "nano" uptake in tumours for instance). A wide range of fluorescent nanoprobes have been designed and tested in preclinical studies for the last few years. They will be reviewed and discussed considering the obstacles that need to be overcome for their potential everyday use in clinics. The conjugation of fluorescence imaging with the benefits of nanotechnology should open the way to new medical applications in the near future.

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Available from: Isabelle Texier, Mar 27, 2014
    • "However, in order to visualize non-fluorescent NPs using fluorescence-based methods, such NPs should be labeled using fluorescent tags. Growing evidence demonstrates possible toxicity and labeling-induced change in NPs and cellular properties (Coll, 2010; Mérian et al., 2012). Transmission and dark-field microscopy methods face challenges due to low sensitivity of absorption measurements and the presence of light scattering artifacts among cells. "
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    ABSTRACT: Growing biomedical applications of non-fluorescent nanoparticles (NPs) for molecular imaging, disease diagnosis, drug delivery, and theranostics require new tools for real-time detection of nanomaterials, drug nano-carriers, and NP-drug conjugates (nanodrugs) in complex biological environments without additional labeling. Photothermal (PT) microscopy (PTM) has enormous potential for absorption-based identification and quantification of non-fluorescent molecules and NPs at a single molecule and 1.4 nm gold NP level. Recently, we have developed confocal PTM providing three-dimensional (3D) mapping and spectral identification of multiple chromophores and fluorophores in live cells. Here, we summarize recent advances in the application of confocal multicolor PTM for 3D visualization of single and clustered NPs, alone and in individual cells. In particular, we demonstrate identification of functionalized magnetic and gold–silver NPs, as well as graphene and carbon nanotubes in cancer cells and among blood cells. The potential to use PTM for super-resolution imaging (down to 50 nm), real-time NP tracking, guidance of PT nanotherapy, and multiplex cancer markers targeting, as well as analysis of non-linear PT phenomena and amplification of nanodrug efficacy through NP clustering and nano-bubble formation are also discussed.
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    • "e l s e v i e r . c o m / l o c a t e / e j p b dye used for medical imaging since years [14], and its encapsulation in different nanosystems has been described with however no spectacular achievements since now [15] [16] [17] [18]. "
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    ABSTRACT: Two near infrared cyanine dyes, DiD (1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine perchlorate) and ICG (Indocyanine Green) were loaded in lipid nanoparticles (LNP). DiD-LNP and ICG-LNP presented similar physicochemical characteristics (hydrodynamic diameter, polydispersity, zeta potential), encapsulation efficiency, and colloidal stability when stored in PBS buffer. However, whereas DiD had similar biodistribution than cholesteryl-1-(14)C-oleate ([(14)C]CHO, a constituent of the nanoparticle used as a reference radiotracer), ICG displayed a different biodistribution pattern, similar to that of the free dye, indicative of its immediate leakage from the nanovector after blood injection. NMR spectroscopy using Proton NOE (Nuclear Overhauser Effect) measurements showed that the localization of the dye in the lipid nanoparticles was slightly different: ICG, more amphiphilic than DiD, was found both inside the lipid core and at particle interface, whereas DiD, more hydrophobic, appeared exclusively located inside the particle core. The ICG release rate from the particles was 7% per 1 month under storage conditions (4°C, dark, 10% of lipids), whereas no leakage could be detected for DiD. ICG leakage increased considerably in the presence of BSA 40 g/L (45% leakage in 24 h at 100 mg/mL of lipids), because of the high affinity of the fluorophore for plasma proteins. On the contrary, no DiD leakage was observed, until high dilution of the nanoparticles which triggered their dissociation (45% leakage in 24 h at 1 mg/mL of lipids). Altogether, the subtle difference in dye localization into the nanoparticles, the partial dissociation of the LNP in diluted media, and more importantly the high ICG affinity for plasma proteins, accounted for the differences observed in the fluorescence biodistribution after tail vein injection of the dye-loaded nanoparticles. Copyright © 2015. Published by Elsevier B.V.
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    • "To track the nanoparticles in vivo, near-infrared fluorescence (NIRF) optical imaging in the range of 650–900 nm [21] is an appropriate technology due to its low autofluorescence and the high penetration depth of the NIR light. Interestingly, the use of nanoparticles as carrier systems for NIRF-emitting dyes was shown to improve their admission, prolong their circulation time in the body, intensify their fluorescence and improve their photostability [22] [23] [24]. Among the different nanoparticle varieties currently available, calcium phosphate nanoparticles are very attractive [25] [26] [27] [28] [29] [30] [31] as they exhibit high biocompatibility, small size, low toxicity, high biodegradability, easy preparation and suitability for functionalization [32]. "
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