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For bioimaging purposes, non-cytotoxic fluorescent labels, stable in biological media and capable of site-specific labeling are in upsurging demand. However, many fluorescent dyes with promising properties, such as fluorescent organic dyes, are poorly water-soluble and often lose their properties in water, limiting their use for bioapplications. The weak signals, poor photobleaching resistance, short fluorescence life time and low chemical stability are continuous challenges for the development of optimal fluorescent probes.
The use of aqueous colloidal structures, such as nanovesicles, as nanocarriers for the loading of the organic dyes offers a promising strategy to overcome this limitation. As a matter of fact, we have engineered a new class of fluorescent organic nanoparticles (FONs) using thermodynamically stable nanovesicles named quatsomes (QS) [1-4]. QSs are new class of exceptionally stable small unilamellar vesicles with sizes smaller than 100nm, and formed by the self-assembly of sterols and quaternary ammonium surfactants. [5,6] Dye-loaded QSs can be prepared by a one-step method using compressed CO2, named depressurization of expanded liquid organic solution-suspension (DELOS-susp).[7] Indeed, it is a green technology leading to a formation of a highly homogenous dispersion of nanovesicles stables in an aqueous environment. The loading of water-insoluble carbocyanines dyes into QSs, has successfully proved the photostability of the obtained FONs in aqueous solutions, as well as, their valuable brightness [6]. They show excellent colloidal stability and structural homogeneity along with superior optical properties, in comparison with the fluorophores in solution.
Dye-loaded QSs have enhanced optical properties, demonstrating the absence of non-fluorescent aggregates due to the Aggregation Caused Quenching (ACQ) effect, neither the formation of J- and H-aggregates was produced, in contrary to the well-known tendency of cyanines to aggregate [8]. Different methods for obtaining dye loaded nanoparticles were compared pointing the advantages of dye-loaded QS over other dye-based FONs, in terms of both, optical and colloidal properties. The effect of the dye loading on the physicochemical properties were studied as well as the brightness, showing higher brightness when dyes were located at the QS membrane. Moreover, experimental results were supported by molecular dynamics (MD) simulations which give information on the configuration of the dyes within the membrane. The potential of dye-loaded QSs for biological imaging was studied using a superresolution microscopy technique, the stochastic optical reconstruction microscopy (STORM).
This study determine that dye-based QS are remarkable candidates as nanostructured probes for biological imaging, not only because of their photophysical properties but also, for their capabilities to be precisely decorated at their surfaces with targeting groups3 and to integrate small drugs or large biomolecules. All such benefits represent a certainly promising probe for bioimaging and, especially, for theragnostic nanomedicine.
1. Elizondo, E. et al. Influence of the Preparation Route on the Supramolecular Organization of Lipids in a Vesicular System. J. Am. Chem. Soc. 134, 1918–1921 (2012).
2. Ferrer-Tasies, L. et al. Quatsomes: Vesicles Formed by Self-Assembly of Sterols and Quaternary Ammonium Surfactants. Langmuir 29, 6519–6528 (2013).
3. Cabrera, I. et al. Multifunctional Nanovesicle-Bioactive Conjugates Prepared by a One-Step Scalable Method Using CO2-Expanded Solvents. Nano Lett. 13, 3766–3774 (2013).
4. Grimaldi, N. et al. Lipid-based nanovesicles for nanomedicine. Chem. Soc. Rev. 45, 6520–6545 (2016).
5. Silbaugh, D. A. et al. Highly Fluorescent Silicon Nanocrystals Stabilized in Water Using Quatsomes. Langmuir 33, 14366–14377 (2017).
6. Antonio, A. et al. Nanostructuring Lipophilic Dyes in Water Using Stable Vesicles, Quatsomes, as Scaffolds and Their Use as Probes for Bioimaging. Small 14, 1703851 (2018).
7. Ventosa, Nora; Veciana, Jaume; Sala, Santiago; Cano, M. Method for Obtaining Micro- and Nano-disperse systems. (2006). doi:WO/2006/079889
8. Gadde, S., Batchelor, E. K. & Kaifer, A. E. Controlling the Formation of Cyanine Dye H- and J-Aggregates with Cucurbituril Hosts in the Presence of Anionic Polyelectrolytes. Chem. – A Eur. J. 15, 6025–6031 (2009).
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