Article

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

ABSTRACT 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.

Download full-text

Full-text

Available from: Isabelle Texier, Mar 27, 2014
1 Follower
 · 
159 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Photodynamic therapy (PDT) of tumors causes skin photosensitivity as a result of unspecific accumulation behavior of the photosensitizers. PDT of tumors was improved by calcium phosphate nanoparticles conjugated with 1) mTHPC as photosensitizer, 2) the RGDfK-peptide for favored tumor targeting, and 3) the fluorescent dye molecule DY682-NHS for enabling near-infrared fluorescence (NIRF) optical imaging in vivo. The nanoparticles were characterized concerning size, spectroscopic properties, and uptake into CAL-27 cells. The nanoparticles had a hydrodynamic diameter of approximately 200 nm and a zeta potential of around +22 mV. Their biodistribution at 24 h after injection was investigated via NIRF optical imaging. After treating tumor-bearing CAL-27 mice with nanoparticle-PDT, the therapeutic efficacy was assessed by a fluorescent DY-734-annexin V probe at 2 days and 2 weeks after treatment to detect apoptosis. Additionally, the contrast agent IRDye(®) 800CW RGD was used to assess tumor vascularization (up to 4 weeks after PDT). After nanoparticle-PDT in mice, apoptosis in the tumor was detected after 2 days. A decrease of tumor vascularization as well as of tumor volume was detected in the next days after PDT. Calcium phosphate nanoparticles can be used as multifunctional tools for NIRF optical imaging, PDT, and tumor targeting as they exhibited a high therapeutic efficacy, were capable of inducing apoptosis and destroying tumor vascularization. Copyright © 2014. Published by Elsevier Ltd.
    Acta Biomaterialia 12/2014; 14. DOI:10.1016/j.actbio.2014.12.009 · 5.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the last several decades, development of various imaging techniques such as computed tomography, magnetic resonance imaging, and positron emission tomography greatly facilitated the early detection of cancer. Another important aspect that is closely related to the survival of cancer patients is complete tumor removal during surgical resection. The major obstacle in achieving this goal is to distinguish between tumor tissue and normal tissue during surgery. Currently, tumor margins are typically assessed by visual assessment and palpation of the tumor intraoperatively. However, the possibility of microinvasion to the surrounding tissues makes it difficult to determine an adequate tumor-free excision margin, often forcing the surgeons to perform wide excisions including the healthy tissue that may contain vital structures. It would be ideal to remove the tumor completely, with minimal safety margins, if surgeons could see precise tumor margins during the operation. Molecular imaging with optical techniques can visualize the tumors via fluorophore conjugated probes targeting tumor markers such as proteins and enzymes that are upregulated during malignant transformation. Intraoperative use of this technique may facilitate complete excision of the tumor and tumor micromasses located beyond the visual capacity of the naked eye, ultimately improving the clinical outcome and survival rates of cancer patients.
    Current pharmaceutical biotechnology 12/2013; DOI:10.2174/1389201014666131226113300 · 2.51 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 03/2015; 93. DOI:10.1016/j.ejpb.2015.03.019 · 4.25 Impact Factor