SCIENTIFIC HIGHLIGHTS

Stable fluorescent nanovesicles as new probes for bioimaging

New fluorescent nanovesicles have been developed, using compressed C02 technology developed in-house, to produce efficient probes for bioimaging applications

In the frame of a Marie-Curie Initial Training Network (ITN), Nano-2-fun, new fluorescent nanoparticles with superior stability and remarkable optical properties, bearing fluorescent organic dyes, have been developed. These fluorescent nanovesicles have already proved to be efficient probes for in vivo and in vitro imaging and have potential applications as biomarkers in bio-imaging, diagnostic, biomedical applications and theranostics [1](combined therapeutic and diagnostic functionalities). The preparation of the fluorescent nanovesicles offers a great potential for the development of multifunctional nanovesicles integrating for example drugs (such as proteins, small molecules or even genetic material), targeting peptides, and fluorescent imaging agents. Moreover, the fluorescent nanovesicles can incorporate simultaneously several dyes, obtaining probes for more complex applications, such as multicolour imaging. This platform is especially effective for the conveyance of non-water-soluble dyes whose optical properties are usually not stable in physiological media, but remain efficient after incorporation in nanovesicles [2].

Fluorescent nanovesicles, with sizes of less than 100 nm, are prepared by a single-step, robust and easily scalable CO2-based methodology, namely DELOS-SUSP. This process guarantees superior structural homogeneity, both regarding size and lamellarity, and reproducibility. The obtained fluorescent nanovesicles, by this methodology, are chemically, physically and optically stable during several months.

The optical properties of the fluorescent dyes, such as brightness and photostability, are maintained and, in some cases, improved by incorporation in the nanovesicles. Simultaneous integration of dyes and active compounds (drugs or bio-active compounds) is possible, forming multifunctional nanovesicles.

These new stable fluorescent nanovesicles have shown excellent features as efficient probes for: in vitro, in vivo and ex vivo imaging. Additionally, fluorescent nanovesicles appear to be promising biosensors in medical devices, embed in Point of Care (POC) devices (used for the analysis of patient’ samples without leaving the consultancy of the doctor) or In Vitro Diagnostic (IVD) tests, for instance.

Authors:
Antonio Ardizzone,1Davide Blasi,1Siarhei Kurhuzenkau,2Danilo Vona,3Sílvia Illa‐Tuset,1,4Arnulf Rosspeintner,5,Jordi Faraudo,Angela Punzi,3Mykhailo Bondar,6,Emiliano Altamura,3David Hagan,7Natascia Grimaldi,1Eric W. Van Stryland,7Anna Painelli,2Cristina Sissa2, Santi Sala,1Natalia Feiner,8Eric Vauthey,5Lorenzo Albertazzi,8Gianluca M. Farinola,3Imma Ratera,1Jaume Veciana,1 Nora Ventosa1.

Affiliations:
1 Institut de Ciències de Materials de Barcelona (ICMAB-CSIC), Spain.
2 Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale Università di Parma, Italy.
3 Dipartimento di Chimica Università degli Studi di Bari Aldo Moro, Italy.
4 Theoretical Sciences Unit, JNCASR, India.
5 Department of Physical Chemistry, University of Geneva, Switzerland.
6 Institute of Physics, National Academy of Sciences of Ukraine, Ukraine.
7 The College of Optics and Photonics (CREOL), University of Central Florida, USA
8 Institute for Bioengineering of Catalonia (IBEC), Parc Cientìfic de Barcelona (PCB), Spain.

Publications:
[1] Highly Stable and Red-Emitting NanovesiclesIncorporatingLipophilic Diketopyrrolopyrroles for Cell Imaging, 
Chemistry a European Journal 24, 11386 - 11392 (2018)
DOI: 10.1002/chem.201801444

[2] Nanostructuring Lipophilic Dyes in Water Using Stable Vesicles, Quatsomes, as Scaffolds and Their Use as Probes for Bioimaging
Small 14 1703851 (2018)
DOI: 10.1002/smll.201703851

Figure:
Example of the use of the new developed fluorescent nanovesicles, embed in an in vitro diagnostic assay, specifically an organ-on-chip simulating endothelial cells environment.

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