Fluorescent Organic Nanoparticles Research Articles

Facile synthesis of inorganic–organic hybrid fluorescent nanoparticles with AIE feature using hexachlorocyclotriphosphazene as the bridge

In recent 20 years, the functional materials with aggregation-induced emission (AIE) feature have shown huge superiority and great potential in biomedicine field and numerous strategies have been developed to fabricate these AIE-active functional materials. Though delightful developments, facile synthesis of inorganic–organic hybrid fluorescent nanoparticles with AIE feature has seldom reported thus far. In this work, we reported for the first time that novel cross-linked inorganic–organic hybrid polyphosphazene nanospheres with AIE feature could be simply synthesized via conjugation AIE-active fluorophore tetraphenylethylene derivative (TPE-NH2) with hydrophilic polyethylene glycol (PEG-NH2) using hexachlorocyclotriphosphazene (HCCP) as the bridge. This strategy is simple and high-efficient with some advantages (e.g., the reaction can occur under room temperature, the reaction time is short, no surfactant is required and no air-protection is needed). The structure, morphology and spectroscopic properties of TPE-HCCP-PEG nanoparticles (NPs) were characterized by various apparatus. To further evaluate their potential applications in biomedical fields, biocompatibility and cell uptake behavior of TPE-HCCP-PEG composites have been examined. Results demonstrated that TPE-HCCP-PEG NPs possessed intensive fluorescence and high water dispersibility and were of low cytotoxicity. These features endow TPE-HCCP-PEG NPs huge potential in fluorescence imaging. Also, the strategy can be extended for the construction of many other inorganic–organic hybrid polymers taken advantage of their unique features and convenient synthetic method. We expect that this work will open a new avenue for the synthesis of inorganic heterocycles centered AIE-active materials with extensive application prospects.

A polymerizable Aggregation Induced Emission (AIE)-active dye with remarkable pH fluorescence switching based on benzothiazole and its application in biological imaging

In recent years, Aggregation Induced Emission (AIE)-active fluorescent materials have been attracting considerable attention because they play an important role in clinical medicine, photoelectricity, environmental science, biological imaging, and sensors. In this contribution, a novel tetraphenylethylene (TPE) derivative of 2-(4-(1,2,2-triphenylvinyl)benzene) benzothiazole methacrylate (TPBMA) monomer was synthesized by a Suzuki coupling and an acylation reaction using TPE and benzothiazole as structural units, whose maximum emission wavelength respectively appeared at 506 nm in neutral medium and 579 nm in acidic medium with excellent pH sensitivity, and it could change repeatedly at 500 nm and 579 nm under HCl/NH3 fuming, indicating the reversible fluorescence conversion property. As compared with the TPB dye, the emission wavelength of TPBMA spectra has an obvious red-shift, which is consistent with the transition energy level difference (△E) of highest occupied molecular orbital (HOMO) and lowest unoccupied orbital (LUMO) situation by quantum chemistry calculation. Subsequently, the copolymers PEG-TB were successfully prepared by RAFT polymerization of TPBMA and poly (ethylene glycol) monomethacrylate (PEGMA), and their molecular weight (Mw) was about 2.12 × 104 with a narrow polydispersity index (PDI). From the 1H NMR analysis, the actual fraction of TPBMA in the PEG-TB copolymers increased to 22.6% from 17.4% when the feed ratio of TBMTA changed to 25.0% from 20.0%. The obtained PEG-TB could self-assemble into fluorescent organic nanoparticles (FONs) with 100–150 nm diameter in aqueous solution, and their fluorescence intensity increased gradually with the increase of water fraction in the THF solution, indicating the obvious AIE behavior. Moreover, the as-prepared PEG-TB FONs exhibited the prospective potential in the field of biological imaging due to their low cytotoxicity, excellent biocompatibility and easy cells absorption.

Progress and trends in self-assembly driven fluorescent organic nanoparticles: A brief overview

Organic nanoparticles have recently attracted increasing attention in diverse field of applications in materials, sensing, biomedicine and others due to their extraordinary physico-optical properties and facile synthesis. These π-conjugated small organic molecules exhibit aggregation induced emission (AIE) property, photo/physical stability, good cytocompatibility as well as biodegradability and easy surface modulation ability. In this mini-review, we have summarized the progress and trends in the area of development of organic nanoparticles from π-conjugated small organic molecule. Some typical as well as few unconventional examples of AIE active systems are discussed and also focussed on their structure-property relationship to exhibit unique photophysical characteristics. To decipher the mechanistic aspect of AIE phenomenon, systematic structural design strategies are also discussed. Finally, development of optoelectronic devices, sensors, bioimaging probes, therapeutic agents, and AIE-active luminogens are exemplified with high tech innovations.

Water-soluble AIE-active Fluorescent Organic Nanoparticles: Design, Preparation and Application for Specific Detection of Cyanide in Water and Food Samples.

A dilactosyl-dicyanovinyl-functionalized tetraphenylethene (TPELC) was designed, synthesized and used for ratiometric sensing of cyanide. TPELC was comprised of three moieties (tetraphenylethylene, dicyanovinyl group and lactose unit) in one molecule, making TPELC water-soluble and aggregation-induced emission (AIE)-active and selectively reactive to cyanide. Compared with other reported fluorescent probes containing dicyanovinyl group, TPELC is the first AIE luminogen to be assembled as fluorescent organic nanoparticles (FONs) for sensing of cyanide in water without the use of surfactant or the help of organic solvents based on the nucleophilic addition reaction. The detection mechanism was verified by liquid chromatograph mass spectrometry experiments and by protonation of cyanide to reduce the nucleophilicity of cyanide. In addition, TPELC was used for detection of the cyanide content of food samples and test strips were developed to simplify the detection procedure.

Starlike polymer brush-based ultrasmall nanoparticles with simultaneously improved NIR-II fluorescence and blood circulation for efficient orthotopic glioblastoma imaging

Fluorescence imaging (FI) in the second near-infrared region (NIR-II, 1000–1700 nm) has attracted great attention for brain tumor imaging due to its deep penetration and high resolution. However, traditional NIR-II organic fluorescent nanoparticles (NPs) are usually hindered by uncontrolled large size (~30–100 nm), marked aggregation-caused quenching (ACQ) effect, and limited blood circulation (~1–3 h), which have great impact on efficient NIR-II FI of deep brain tumors. Herein, starlike polymer brush-based ultrasmall TQFP-10 NPs, with bright NIR-II fluorescence, prolonged blood circulation, and enhanced tumor accumulation, are facilely prepared for efficient orthotopic glioblastoma (GBM) imaging. Compared with traditional method prepared NPs (physically coated TQF@NPs and PEG modified TQF-PEG5K NPs), the ultrasmall (~8 nm) TQFP-10 NPs display a higher NIR-II fluorescence QY (1.9%), which is 2.1- and 3.8-fold higher than TQF@NPs (0.9%) and TQF-PEG5K NPs (0.5%), respectively. In addition, TQFP-10 NPs present a 10.6-fold higher blood circulation half-life (t1/2 = 8.5 h) than that of TQF-PEG5K NPs. Consequently, TQFP-10 NPs exhibit 4.2- and 33-fold higher maximal tumor to normal tissue ratio in subcutaneous and in situ NIR-II FI of GBM, respectively, than TQF@NPs and TQF-PEG5K NPs, attractively realizing GBM imaging. This work provides a general strategy for constructing ultrasmall NIR-II fluorescent NPs with simultaneously improved NIR-II fluorescence and blood circulation for efficient brain tumor imaging.

Synthesis of novel benzothiazole based fluorescent and redox-active organic nanoparticles for their application as selective and sensitive recognition of Fe3+ ions

A novel benzothiazole based compound (1) has been synthesized and further employed for the fabrication of fluorescent as well as redox active organic nanoparticles (1-ONPs) by adopting a nano-re-precipitation method. The formation of 1-ONPs was confirmed by Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM) techniques, where the size was found to be ~42.84 nm in the optimized conditions. The resulting 1-ONPs acted as selective and sensitive sensor for recognition of Fe3+ ions in dual transduction mode. The nanoparticles underwent quenching of fluorescence intensity as well as an amplified stripping current response in the presence of Fe3+. The high surface charge density worked as a tool for enhancing the current response of nanoparticles over bulk solution mode and hence is extended to in-field analysis.

A Bottom-Up Approach to Red-Emitting Molecular-Based Nanoparticles with Natural Stealth Properties and their Use for Single-Particle Tracking Deep in Brain Tissue.

Fluorescent nanoparticles dedicated to bioimaging applications should possess specific properties that have to be maintained in the aqueous, reactive, and crowded biological environment. These include chemical and photostability, small size (on the scale of subcellular structures), biocompatibility, high brightness, and good solubility. The latter is a major challenge for inorganic nanoparticles, which require surface coating to be made water soluble. Molecular-based fluorescent organic nanoparticles (FONs) may prove a promising, spontaneously water-soluble alternative, whose bottom-up design allows for the fine-tuning of individual properties. Here, the critical challenge of controlling the interaction of nanoparticles with cellular membranes is addressed. This is a report on bright, size-tunable, red-emitting, naturally stealthy FONs that do not require the use of antifouling agents to impede interactions with cellular membranes. As a proof of concept, single FONs diffusing up to 150µm deep in brain tissue are imaged and tracked.

Photoinduced Architectural Transformation of Noncovalent Fluorescent Photochromic Organic Nanoparticles as Evidenced by Amplified Fluorescence Photoswitching

Dual nanoparticles endowed with emission photoswitching ability are produced by the flash coprecipitation of fluorophores and photochromes in water in order to investigate the mutual interplay between the self-assembled photoactive units as a function of their respective ratio. Photophysical studies show that high fluorophore/photochrome ratios favor very fast on/off fluorescence photoswitching, while the opposite is true for recovering emission thanks to the strong antenna effects permitted by the spatially confined entities in nanoparticles. Attempts to regenerate the initial state upon visible irradiation reveal unexpected structural transformations, which result from the noncovalent dye self-assemblies. Morphological investigations support phototriggered photochrome clustering within and around the fluorescent core of the dual nanoparticles after a UV–vis cycle or irradiation, causing partitioning of the photoactive units. The photoinduced morphological changes provide attractive prospects in the fabrication of smart drug delivery systems where active material release by external stimuli represents a very dynamic research area.

Naphthalimide based fluorescent organic nanoparticles in selective sensing of Fe3+ and as a diagnostic probe for Fe2+/Fe3+ transition.

Fluorescent organic nanoparticles (FONPs) have attracted considerable attention as a practical and effective platform for sensing and imaging applications. The present article delineates the fabrication of FONPs derived from the naphthalimide based histidine appended amphiphile, NID. The self-assembly of NID in 99 vol% water in DMSO led to the formation of FONPs through J-type aggregation. Aggregation-induced emission (AIE) was observed due to the pre-associated excimer of NID with bluish green emission at 470 nm along with intramolecular charge transfer (ICT). The emission of NID FONPs was utilized for selective sensing of Fe3+ and bioimaging of Fe3+ inside mammalian cells. The fluorescence intensity of the FONPs was quenched with the gradual addition of Fe3+ due to the formation of a 1 : 1 stoichiometric complex with the histidine residue of NID. The morphology of the FONPs transformed from spherical to spindle upon the complex formation of NID with Fe3+. The limit of detection (LOD) of this AIE based turn-off chemosensor for Fe3+ was found to be 12.5 ± 1.2 μM having high selectivity over other metal ions. On the basis of the very low cytotoxicity and selective sensing of Fe3+, NID FONPs were successfully employed for bioimaging of Fe3+ ions through fluorescence quenching within mammalian cells (NIH3T3, B16F10). Considering the varying oxidative stress inside different cells, NID FONPs were used for detecting Fe2+ to Fe3+ redox state transition selectively inside cancer cells (B16F10) in comparison to non-cancerous cells (NIH3T3). Selective sensing of cancer cells was substantiated by co-culture experiment and flow cytometry. Hence, NID FONPs can be a selective diagnostic probe for cancer cells owing to their higher H2O2 content.

Lipase sensing by naphthalene diimide based fluorescent organic nanoparticles: a solvent induced manifestation of self-assembly.

The precise control of supramolecular self-assembly is gaining utmost interest for the demanding applications of manifested nano-architecture across the scientific domain. This study delineates the morphological transformation of naphthalene diimide (NDI) derived amphiphiles with varying water content in dimethyl sulfoxide (DMSO) and the selective sensing of lipase using its aggregation-induced emission (AIE) properties. To this end, NDI-based, benzyl alcohol protected alkyl chain (C1, C5, and C10) linked amphiphilic molecules (NDI-1,2,3) were synthesized. Among the synthesized amphiphiles, benzyl ester linked C5 tailored naphthalene diimide (NDI-2) exhibited AIE with an emission maximum at 490 nm in a DMSO-water binary solvent system from fw = 30% and above water content. The fibrous morphology of NDI-2 at fw = 30% got gradually transformed to spherical aggregated particles along with steady increment in the emission intensity upon increasing the amount of water in DMSO. At fw = 99% water in DMSO, complete transformation to fluorescent organic nanoparticles (FONPs) was observed. Microscopic and spectroscopic techniques demonstrated the solvent driven morphological transformation and the AIE property of NDI-2. Moreover, this AIE of NDI-2 FONPs was employed in the selective turn-off sensing of lipase against many other enzymes including esterase, through hydrolysis of a benzyl ester linkage with a limit of detection 10.0 ± 0.8 μg L-1. The NDI-2 FONP also exhibited its lipase sensing efficiency in vitro using a human serum sample.

Single component photoresponsive fluorescent organic nanoparticles: a smart platform for improved biomedical and agrochemical applications.

In the last two decades, light responsive nano drug delivery systems (DDSs) have gained considerable importance, particularly in the area of biology and medicine. In general, light responsive nano DDSs are bicomponent and constructed using two ingredients, namely a nanocarrier and a phototrigger. The synthesis of these bicomponent nano DDSs requires multiple steps, which limits their applications. Hence, we have reported single component light responsive nano DDSs using fluorescent organic nanoparticles (FONPs) which acted both as a nanocarrier and a phototrigger. This feature article provides an overview of recently developed light responsive single component FONPs and their applications in the regulated release of anticancer drugs, gasotransmitters, antibacterial agents, and pesticides, and also as efficient PDT agents. We have summarised the synthesis, characterisation, and photophysical, photochemical, and in vitro behaviours of these light responsive FONPs. In addition, we also discussed the advantages of using FONPs as a nano DDS for cellular studies like: excellent biocompatibility, efficient cellular internalisation, real time monitoring of the drug release ability inside the cells, and enhanced cytotoxicity due to regulated release of bioactive molecules inside the cells.

Self-assembling, structure and nonlinear optical properties of fluorescent organic nanoparticles in water.

Owing to their intense emission, low toxicity and solubility in aqueous medium, fluorescent organic nanoparticles (FONs) have emerged as promising alternatives to inorganic ones for the realization of exogenous probes for bioimaging applications. However, the intimate structure of FONs in solution, as well as the role played by intermolecular interactions on their optical properties, remains challenging to study. Following a recent Second-Harmonic Scattering (SHS) investigation led by two of us [Daniel et al., ACS Photonics, 2015, 2, 1209], we report herein a computational study of the structural organization and second-order nonlinear optical (NLO) properties of FONs based on dipolar chromophores incorporating a hydrophobic triphenylamine electron-donating unit and a slightly hydrophilic aldehyde electron-withdrawing unit at their extremities. Molecular dynamics simulations of the FON formation in water are associated with quantum chemical calculations, to provide insight into the molecular aggregation process, the molecular orientation of the dipolar dyes within the nanoparticles, and the dynamical behavior of their NLO properties. Moreover, the impact of intermolecular interactions on the NLO responses of the FONs is investigated by employing the tight-binding version of the recently developed simplified time-dependent density functional theory (sTD-DFT) approach, allowing the all-atom quantum mechanics treatment of nanoparticles.

Organic fluorescent nanoparticles using fluorophores synthesized from low-temperature calcination process

Organic fluorescent nanoparticles have attracted increasing interests in various fields including sensing, imaging and therapy, owing to their excellent optical properties and biocompatibility. However, the chemical synthesis of organic fluorophores is always a complicated, tedious and time-consuming process. Herein, we fabricated fluorophores through one-step calcination at relatively low temperature (370 °C), which possessed satisfying fluorescence quantum yield of about 30 % and good solubility in organic solvent. Using these emissive material without special purification procedure, organic fluorescent nanoparticles were obtained through a facile reprecipitation method in the presence of Saponin, a naturally amphiphilic surfactant. The obtained fluorescent nanoparticle was demonstrated to possess low toxicity and good cell permeabilization behavior, as well as an excellent performance on cellular imaging. Overall, we provide a facile and low-cost way to prepare the organic fluorescent nanoparticle, which might be a promising candidate for various chemical and biological applications.

Microfluidic Assisted Flash Precipitation of Photocrosslinkable Fluorescent Organic Nanoparticles for Fine Size Tuning and Enhanced Photoinduced Processes.

Highly concentrated dispersions of fluorescent organic nanoparticles (FONs), broadly used for optical tracking, bioimaging and drug delivery monitoring, are obtained using a newly designed micromixer chamber involving high impacting flows. Fine size tuning and narrow size distributions are easily obtained by varying independently the flow rates of the injected fluids and the concentration of the dye stock solution. The flash nanoprecipitation process employed herein is successfully applied to the fabrication of bicomposite FONs designed to allow energy transfer. Considerable enhancement of the emission signal of the energy acceptors is promoted and its origin is found to result from polarity rather than steric effects. Finally, we exploit the high spatial confinement encountered in FONs and their ability to encapsulate hydrophobic photosensitizers to induce photocrosslinking. An increase in the photocrosslinked FON stiffness is evidenced by measuring the elastic modulus at the nanoscale using atomic force microscopy. These results pave the way toward the straightforward fabrication of multifunctional and mechanically photoswitchable FONs, opening novel opportunities in sensing, multimodal imaging, and theranostics.

Aggregation-induced emission-active hyperbranched polymer-based nanoparticles and their biological imaging applications

Herein, we developed a facile one-pot approach to prepare amphiphilic aggregation-induced emission (AIE)-active hyperbranched fluorescent nanoparticles with a core–shell structure. This was conducted via the addition reaction between tetraphenylethylene (TPE)-OH, isophorone diisocyanate, and hyperbranched polyglycidol (HPG) using a one-pot method. The resultant AIE-active hyperbranched polymer structure was characterized by 1H nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The amphiphilic AIE-active polymer was prone to self-assemble in an aqueous solution to form core–shell type nanoparticles with a TPE core and hydroxyl groups on the core surface. The self-assembly of nanoparticles in the aqueous solution was characterized using dynamic light scattering, ultraviolet–visible spectroscopy, fluorescence spectroscopy, and transmission electron microscopy. Aggregation behavior of TPE-HPG polymer in water and diethyl ether was studied by dissipative particle dynamics simulation. Furthermore, these TPE-HPG nanoparticles exhibited a strong blue luminescence in the aqueous solution due to the aggregation of the AIE feature of TPE. These polymeric nanoparticles showed high water solubility, good photostability, and biological imaging properties. The cell viability assay and confocal microscopy imaging results suggested that the TPE-HPG fluorescent polymeric organic nanoparticles (FPNs) have low cytotoxicity and excellent biocompatibility. Thus, TPE-HPG FPNs are excellent candidates for biomedical applications.

Stealth and Bright Monomolecular Fluorescent Organic Nanoparticles Based on Folded Amphiphilic Polymer.

Fluorescent nanoparticles (NPs), owing to their superior brightness, are an attractive alternative to organic dyes. However, their cellular applications remain limited because of their large size, poor homogeneity, and nonspecific interactions in biological media. Herein, we propose a concept of monomolecular fluorescent organic nanoparticles of high brightness and very small size (10-14 nm) built of a single amphiphilic polymer bearing specially designed fluorescent dyes. We found that high PEGylation of poly(maleic anhydride-alt-1-octadecene (PMAO) favors a single-chain polymer folding into monomolecular stealth NPs with highly reduced nonspecific interactions with proteins and live cells. To ensure high stability of our NPs, the fluorophores (BODIPYs) are covalently linked to the polymer through an optimized linker. Among tested linkers of different lengths and polarity, a short medium-polar linker favoring location of the dyes at NPs interface ensures good fluorescence quantum yield and small particle size. The fluorescence brightness of these NPs has been dramatically enhanced by increasing the bulkiness of the BODIPY dyes that prevents their H-aggregation, reaching 2500000 M-1 cm-1 (extinction coefficient × quantum yield). Fluorescence microscopy revealed that the single-particle brightness of these NPs is ∼5-fold higher than that of QDot-585 using the same excitation wavelength (532 nm). Finally, when microinjected inside cells, these small and stealth NPs (10 nm diameter) distribute more evenly than 20 nm QDots inside the cytosol, showing similar spreading as a fluorescent protein. Thus, the developed monomolecular NPs, owing to their small size and stealth properties, are artificial analogues of fluorescent proteins, surpassing the latter >50-fold in terms of brightness.

Amphiphilic AIE-active copolymers with optical activity by chemoenzymatic transesterification and RAFT polymerization: Synthesis, self-assembly and biological imaging

Recently, various AIE-based materials with new characteristics and functions have been developing for different fields. Many chiral polymers are attracting the research interests for the new multifunctional materials in biomedicine, chiral recognition, etc. In this work, novel AIE copolymers with chirality activity were successfully fabricated for the first time. Firstly, a new fluorescent monomer (R)-THM with AIE effect and chirality activity was firstly synthesized by Suzuki reaction and enzymatic transesterification reaction. The quantum yield of (R)-THM increased to 0.643 from 0.100 of its substrate TBP with remarkable red-shift of emission spectra, which was consistent with their quantum chemical calculations of HOMO and LUMO situations, and its specific optical rotation [α]D25°C was about −9.67°. Subsequently, a series of chiral AIE copolymers of PEG-(R)-THM1 and PEG-(R)-THM2 were prepared via RAFT polymerization of (R)-THM and PEGMA with different feeding ratios. Their molecular weights were about 2.0 × 104 g/mol with narrow polydispersity index (PDI), and the kinetics analysis presented a pseudo-first-order linear procedure. For the molar 24.2%–32.3% feeding ratio of (R)-THM, the actual fraction of (R)-THM in the copolymers PEG-(R)-THM1 and PEG-(R)-THM2 was respectively about 22.3% and 30.2%, and the [α]D25°C value of copolymers PEG-(R)-THM1 and PEG-(R)-THM2 was about −2.51° and −3.74°. The amphiphilic structure of the obtained PEG-(R)-THM make them be easily dispersed in water solution and tend to self-assemble into fluorescent organic nanoparticles (FONs) with 100–150 nm diameter by TEM, and their maximum emission wavelength presented at 495 nm with obvious AIE effect. Moreover, the PEG-(R)-THM FONs had good biological compatibility, desirable low cytotoxicity and good cells absorption effect, which showed the great potential in bioimaging application.

Fine Tuning of the HOMO–LUMO Gap of 6‐(Thiophen‐2‐yl) indolizino[3,2‐c]quinolines and their Self‐Assembly to Form Fluorescent Organic Nanoparticles: Rational Design and Theoretical Calculations

AbstractIn this study, we designed and synthesized novel 6‐(thiophen‐2‐yl) indolizino[3,2‐c]quinolines (IQs) guided by density functional theory (DFT) calculations and explored the optical properties of the IQ derivatives together with fractional atomic orbital contribution (FAOC) analysis. In accordance with the DFT predictions, the designed compound, IQ‐C9, with a methoxycarbonyl (MC) group attached to the C9 position of the IQ scaffold, displayed improved fluorescence quantum yields (QY) in solution and in the solid state along with bathochromic shifts compared to previous analogues. TEM images demonstrated that IQ‐C9 forms well‐defined nanoparticle structures (dimensions: 20×50 nm, aspect ratio: 2.3) in aqueous solution. Confocal images of IQ‐C9‐treated MCF7 cells revealed colocalization of IQ‐C9 with lipid droplets, highly dynamic subunits within cells involved in various metabolic disorders and cancers. Our results demonstrated that the analyses based on the FAOC coefficients and molecular orbital (MO) energy levels can be used as a computational method to predict spectral shifts for fluorophores and to design novel fluorescent probes for tracking dynamic cellular processes.

Dye-Loaded Quatsomes Exhibiting FRET as Nanoprobes for Bioimaging.

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.

Small-Molecule Probe for Sensing Serum Albumin with Consequential Self-Assembly as a Fluorescent Organic Nanoparticle for Bioimaging and Drug-Delivery Applications.

The recognition of a specific protein in blood serum amidst similar proteins is a challenging and vital endeavor in clinical diagnostics. Herein, we have described a small-molecule probe (DFPAC-OH) that can induce self-assembly of human serum albumin (HSA) and bovine serum albumin (BSA) to generate a highly sustainable fluorescent organic nanoparticle (NP), useful for imaging and in vitro drug-delivery applications. In the midst of similar proteins, DFPAC-OH selectively binds in a noncovalent manner to serum albumin. The specific binding tailors the fluorescence properties of DFPAC-OH. The lowest detection limit for BSA is 47 nM with a binding constant of 1.03 × 105 M-1. The probe can efficiently detect HSA in an artificial urine sample. Furthermore, the subsequent bovine albumin self-assembled nanoparticle (DFPAC-OH@BSA-NPs) displays a strong emission at 580 nm both in solution and in solid state. The nanoparticle is highly stable over a long pH range, covering the physiologic pH, and shows an excellent bioavailability to be used for sustainable cell imaging and drug-delivery applications. In addition, the cellular internalization and the pH-responsive drug-release behavior of a hydrophobic drug thymoquinone (TQ) encapsulated in DFPAC-OH@BSA-NPs (TQ-DFPAC-OH@BSA-NPs) have also been evaluated in A549 cell lines. The cytotoxic effect and quantification of intracellular reactive oxygen species (ROS) generation were further examined carefully to observe the anticancer property of TQ-DFPAC-OH@BSA-NPs. Therefore, the present system can simultaneously deliver drug molecules and image the event of delivery. The entire nanoparticles are characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), and infrared (IR) spectroscopy. The specific binding of DFPAC-OH is well supported by the molecular docking study, fluorescence lifetime measurement, and circular dichroism analysis.