Suchergebnisse

We present a comprehensive study of two indocarbocyanines, DiI (1,1′-dioctadecyl-3,3,3′3′-tetramethylindocarbocyanine perchlorate) and DiD (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine perchlorate), in water suspensions in the presence of a CTAB surfactant both above and below the critical micellar concentration. The very good affinity of the two dyes with CTAB allows them to be brought into aqueous solutions minimizing aggregation phenomena. When the dyes are loaded inside the micelles, stable fluorescent nanostructures are formed that can be exploited for fundamental studies and for imaging applications. Of special interest are micelles loaded with both dyes: indeed, the large local dye concentration inside the micelles allows observing resonance energy transfer in systems where the global dye concentration is maintained at a low level, so that detailed and robust spectroscopic characterization is possible. Quite impressively, the efficiency of resonance energy transfer is boosted when diluting the sample below the critical micellar concentration. This counterintuitive result is explained in terms of the very large affinity between the dyes and CTAB which favors the dynamical formation of small molecular clusters containing both dyes. Fluorescent micelles are widely used in bioimaging and pharmacokinetic applications. More specifically, the observation of resonant energy transfer in micelles or more generally in nanostructures loaded with two dyes is routinely exploited as a way to assess the nanostructure integrity. In this context, our results demonstrate the importance of robust spectroscopic characterization of the relevant systems in different environments in order to safely assess the viability of the integrity test of nanoparticles based on resonant energy transfer. ; This work is dedicated to Concepció Rovira and Jaume Veciana, inspiring scientists in the field of functional molecular materials. Working with them is a prized privilege and the basis for a solid friendship. AD, MA, FB, CS and AP benefited from the equipment and support of the COMP-HUB Initiative, funded by the "Departments of Excellence" program of the Italian Ministry for Education, University and Research (MIUR, 2018–2022) and acknowledge the support from the high performance computing center at Parma University. JMF, GVN, MK and NV acknowledge support from MINECO through the Severo Ochoa Programme FUNFUTURE (SEV-2015-0496 and CEX2019-000917-S), and the Ministry of Science and Innovation of Spain through the grant PID2019-105622RB-I00 (Mol4Bio), and gratefully acknowledge the financial support received from European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 712949 (TECNIOspring PLUS) and from the Agency for Business Competitiveness of the Government of Catalonia. ; With funding from the Spanish government through the 'Severo Ochoa Centre of Excellence' accreditation (CEX2019-000917-S). ; Peer reviewed

Fluorescent organic nanoparticles (FONs) are emerging as an attractive alternative to the well-established fluorescent inorganic nanoparticles or small organic dyes. Their proper design allows one to obtain biocompatible probes with superior brightness and high photostability, although usually affected by low colloidal stability. Herein, we present a type of FONs with outstanding photophysical and physicochemical properties in-line with the stringent requirements for biomedical applications. These FONs are based on quatsome (QS) nanovesicles containing a pair of fluorescent carbocyanine molecules that give rise to Förster resonance energy transfer (FRET). Structural homogeneity, high brightness, photostability, and high FRET efficiency make these FONs a promising class of optical bioprobes. Loaded QSs have been used for in vitro bioimaging, demonstrating the nanovesicle membrane integrity after cell internalization, and the possibility to monitor the intracellular vesicle fate. Taken together, the proposed QSs loaded with a FRET pair constitute a promising platform for bioimaging and theranostics. ; J.M.F. gratefully thank the financial support received by the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 712949 (TECNIOspring PLUS) and from the Agency for Business Competitiveness of the Government of Catalonia (TECSPR17-1-0035). This work was also financially supported by the Ministry of Economy, Industry, and Competitiveness, Spain, through the "MOTHER" project (MAT2016-80826-R) and the "FLOWERS" project (FUNMAT-FIP-2016) funded by the Severo Ochoa (SEV-2015-0496) awarded to ICMAB. Instituto de Salud Carlos III, through "Acciones CIBER", also supported this work. Characterization of nanovesicles was made at the ICTS "NANBIOSIS", more specifically by the U6 unit of CIBER-BBN. The authors acknowledge the European Commission (EC) FP7-PEOPLE-2013-Initial Training Networks (ITN) "NANO2FUN" project no. 607721 for being the spark that initiated this work. K.B.D. acknowledges support from the National Science Foundation (CBET-1517273 and CHE-1726345). C.S. and A.P. benefited from the equipment and framework of the COMP-HUB Initiative, funded by the "Departments of Excellence" program of the Italian Ministry for Education, University and Research (MIUR, 2018-2022). ; Peer reviewed

The development of artificial vesicles into responsive architectures capable of sensing the biological environment and simultaneously signaling the presence of a specific target molecule is a key challenge in a range of biomedical applications from drug delivery to diagnostic tools. Herein, the rational design of biomimetic DNA-grafted quatsome (QS) nanovesicles capable of translating the binding of a target molecule to amphiphilic DNA probes into an optical output is presented. QSs are synthetic lipid-based nanovesicles able to confine multiple organic dyes at the nanoscale, resulting in ultra-bright soft materials with attractiveness for sensing applications. Dye-loaded QS nanovesicles of different composition and surface charge are grafted with fluorescent amphiphilic nucleic acid-based probes to produce programmable FRET-active nanovesicles that operate as highly sensitive signal transducers. The photophysical properties of the DNA-grafted nanovesicles are characterized and the highly selective, ratiometric detection of clinically relevant microRNAs with sensitivity in the low nanomolar range are demonstrated. The potential applications of responsive QS nanovesicles for biosensing applications but also as functional nanodevices for targeted biomedical applications is envisaged. ; This work was financially supported by the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska- Curie grant agreement "Nano-Oligo Med" (No 778133), Ministry of Science and Innovation (MINECO), Spain, through the "MOL4BIO" project (PID2019-105622RB-I00) and by Instituto de Salud Carlos III (DTS20/00018), Italian Ministry of University and Research (Project of National Interest, PRIN, 2017Y2PAB8_004 through the project "Cutting Edge Analytical Chemistry Methodologies and Bio-Tools to Boost Precision Medicine in Hormone-Related Diseases". M.R. was supported from a Fondazione Umberto Veronesi postdoctoral fellowship. Furthermore, ICMAB-CSIC acknowledges support from the MINECO through the Severo Ochoa Programme for Centers of Excellence in R&D (SEV-2015-0496 and CEX2019-000917-S). Quatsome production and their physicochemical characterization has been performed by the Biomaterial Processing and Nanostructuring Unit (U6) of the ICTS "NANBIOSIS", a unit of the CIBER network in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) located at the Institute of Materials Science of Barcelona (ICMAB-CSIC). ; Peer reviewed

Topical delivery has received great attention due to its localized drug delivery, its patient compliance, and its low risk for side effects. Recent developments have focused on studying new drug delivery systems as a strategy for addressing the challenges of current topical treatments. Here we describe the advances on an innovative drug delivery platform called DELOS nanovesicles for topical drug delivery. Previously, the production of DELOS nanovesicles demonstrated potentiality for the topical treatment of complex wounds, achieving well-tolerated liquid dispersions by this route. Here, research efforts have been focused on designing these nanocarriers with the best skin tolerability to be applied even to damaged skin, and on exploring the feasibility of adapting the colloidal dispersions to a more suitable dosage form for topical application. Accordingly, these drug delivery systems have been efficiently evolved to a hydrogel using MethocelTM K4M, presenting proper stability and rheological properties. Further, the integrity of these nanocarriers when being gellified has been confirmed by cryo-transmission electron microscopy and by Förster resonance energy transfer analysis with fluorescent-labeled DELOS nanovesicles, which is a crucial characterization not widely reported in the literature. Additionally, in vitro experiments have shown that recombinant human Epidermal Growth Factor (rhEGF) protein integrated into gellified DELOS nanovesicles exhibits an enhanced bioactivity compared to the liquid form. Therefore, these studies suggest that such a drug delivery system is maintained unaltered when hydrogellified, becoming the DELOS nanovesicles-based hydrogels, an advanced formulation for topical use. ; This research was funded by Industrial Doctorates Plan of Agaur-Generalitat de Catalunya (2018 DI 057). This work was also co-financed by European Regional Development Funds from the European Union within the framework of the operative FEDER program in Catalonia 2014–2020, by the specific project NANONAFRES ...