6 research outputs found
Croconaine-based nanoparticles enable efficient optoacoustic imaging of murine brain tumors
Contrast enhancement in optoacoustic (photoacoustic) imaging can be achieved with agents that exhibit high absorption cross-sections, high photostability, low quantum yield, low toxicity, and preferential bio-distribution and clearance profiles. Based on advantageous photophysical properties of croconaine dyes, we explored croconaine-based nanoparticles (CR780RGD-NPs) as highly efficient contrast agents for targeted optoacoustic imaging of challenging preclinical tumor targets. Initial characterization of the CR780 dye was followed by modifications using polyethylene glycol and the cancer-targeting c(RGDyC) peptide, resulting in self-assembled ultrasmall particles with long circulation time and active tumor targeting. Preferential bio-distribution was demonstrated in orthotopic mouse brain tumor models by multispectral optoacoustic tomography (MSOT) imaging and histological analysis. Our findings showcase particle accumulation in brain tumors with sustainable strong optoacoustic signals and minimal toxic side effects. This work points to CR780RGD-NPs as a promising optoacoustic contrast agent for potential use in the diagnosis and image-guided resection of brain tumors
Designing artificial fluorescent proteins: Squaraine-LmrR biophosphors for high performance deep-red biohybrid light-emitting diodes
Biophosphors with fluorescent proteins (FPs) are promising candidates to replace rare-earth color down-converting filters for white light-emitting diodes (LEDs). There is, however, a lack of deep-red FPs meeting high photostabilities, photoluminescence quantum yields (Ï), and throughput expression yields. Herein, a new approach for the design of highly emissive and stable deep-red biophosphors combining an artificial FP (Lactococcal multidrug resistance Regulator (LmrR) as protein host and an archetypal red-emitting squaraine (S) as guest) with a polymer network is demonstrated toward high performing deep-red biohybrid LEDs (Bio-HLEDs). At first, the best protein pocket (aromaticity, polarity, charge, etc.) to stabilize S in water is determined using four LmrR variants (position 96 with tryptophan, histidine, phenylalanine, and alanine). Computational and time-resolved spectroscopic findings suggest that the tryptophan is instrumental toward achieving artificial red-emitting FPs with Ï > 50% stable over weeks. These features are further enhanced in the polymer coating (Ï > 65% stable over months) without affecting emission color. Finally, deep-red Bio-HLEDs are fabricated featuring external quantum efficiencies of 7% and stabilities of â800 h. This represents threefold enhancement compared to reference devices with S-polymer color filters. Overall, this work highlights a new design for highly emissive deep-red biophosphors, achieving record performance in deep-red protein-LEDs.The authors acknowledge the European Union's Horizon 2020 research and innovation FET-OPEN under grant agreement ARTIBLED No. 863170. R.D.C. acknowledges the ERC-Co InOutBioLight No. 816856. P.B.C. acknowledges financial support from the Ministry of Science, Innovation and Universities of Spain under the Beatriz Galindo Programme (No. MCIU-19-BEAGAL 18/0224), from MCIN/AEI/10.13039/501100011033 grant No. PGC2018-095953-B-I00 and from the Technical University of Munich (TUM) under the TUM Global Visiting Professor Programme. A.L.C. acknowledges support by the European Research Council ERC-CoG-648071-ProNANO and ERC-PoC-841063-NIMM; and Agencia Estatal de InvestigaciĂłn, Spain (No. PID2019-111649RB-I00). This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency Grant No. MDM-2017-0720 (CIC biomaGUNE).Peer reviewe
Homopolymeric Protein Phosphors: Overpassing the Stability Frontier of Deep-Red Bio-Hybrid Light-Emitting Diodes
<p>Although protein-polymer phosphors are an emerging photon-management filter concept for hybrid light-emitting diodes, deep-red-emitting devices based on archetypal fluorescent proteins (FPs; mCherry) are still poorly performing with lifetimes <50 h under high photon-flux excitation and ambient conditions. Here, the challenge is two-fold: i) understanding the deactivation mechanism of red-emitting FP-polymer coatings and, in turn, ii) identifying the best polymer design for highly stable devices. This study first provides comprehensive photophysical/thermal/structural studies and device degradation (ambient/inert) analysis, revealing the presence of photo-induced cisâtrans isomerization and the effect of oxygen and water on the deactivation of mCherry in reference polymer coatings. Based on these findings, a new bio-phosphor configuration using polyvinyl alcohol derivatives, in which crystallinity and amount of trapped water (stiffness and oxygen/moisture barriers) are easily controlled by the hydroxylation degree, is successfully achieved. Compared to the prior art, these devices significantly outperform the reference stability (>50-fold enhancement), showing a brightness loss of <5% over the first 2000 h and a final device lifetime of 2600 h. Hence, this study describes a unique rationale toward designing polymers to stabilize FPs for lighting, overpassing stability frontiers in deep-red hybrid light-emitting diodes (HLEDs) going from hours to months.</p>
Bacterial outer membrane vesicles as cationic dye carriers for optoacoustics-guided phototherapy of cancer
Abstract Background Cationic dyes are widely used as biomarkers for optical imaging. However, most of these are hydrophobic and cannot be employed in vivo without chemical conjugation or modification. Herein, we report for the first time the use of bacterial outer membrane vesicles (OMVs) as nanocarriers of cationic dyes for cancer theranostics. Results We demonstrate that cationic dyes (IR780, Cy7, and Cy7.5) form stable complexes with negatively charged bacterial-OMVs, improving the dyesâ in vivo circulation and optoacoustic properties. Such OMV-Dye complexes are biodegradable and safe for in vivo applications. Importantly, this method of cationic dye loading is faster and easier than synthetic chemistry approaches, and the efficient tumor accumulation of OMV-Dyes enables sensitive tumor detection using optoacoustic technology. As a proof-of-concept, we generated OMV-IR780 for optoacoustics-guided in vivo tumor phototherapy in a mouse model. Conclusions Our results demonstrate cationic dye-bound OMVs as promising novel nanoagents for tumor theranostics
Challenging a Preconception: Optoacoustic Spectrum Differs from the Optical Absorption Spectrum of Proteins and Dyes for Molecular Imaging
CoreâShell Structured Fluorescent Protein Nanoparticles: New Paradigm Toward ZeroâThermalâQuenching in HighâPower Biohybrid LightâEmitting Diodes
Abstract Stable and efficient highâpower biohybrid lightâemitting diodes (BioâHLEDs) using fluorescent proteins (FPs) in photon downconverting filters have not been achieved yet, reaching best efficiencies of 130 lm Wâ1 stable for >5 h. This is related to the rise of the device temperature (70â80 °C) caused by FPâmotion and quick heatâtransmission in waterâbased filters, they lead to a strong thermal emission quenching followed by the quick chromophore deactivation via photoinduced Hâtransfer. To tackle both issues at once, this work shows an elegant concept of a new FPâbased nanoparticle, in which the FP core is shielded by a SiO2âshell (FP@SiO2) with no loss of the photoluminescence figuresâofâmerit over years in foreign environments: dry powder at 25 °C (ambient) or constant 50 °C, as well as suspensions in organic solvents. This enables the preparation of waterâfree photon downconverting coatings with FP@SiO2, realizing onâchip highâpower BioâHLEDs with 100 lm Wâ1 stable for >120 h. Both thermal emission quenching and Hâtransfer deactivation are suppressed, since the device temperature holds 100 h). Hence, FP@SiO2 is a new paradigm toward waterâfree zeroâthermalâquenching biophosphors for firstâclass highâpower BioâHLEDs