Liposome Based Near-Infrared Sensors for the Selective Detection of Hydrogen Sulfide.

Cyanine dye-based new amphiphilic compound NIR-Amp has been synthesised. NIR-Amp was embedded with phospholipids DOPC and DPPC to form liposomes based nanoscale chemical sensors NIR-Lip1 and NIR-Lip2. Here, two different phospholipids were used to demonstrate the influence of lipid structure, composition and fluidity on sensing of nanosensors. Both the probes show NIR absorption maximum at 790 nm and emission maximum at 815 nm. H2 S-triggered thiolation resulted a remarkable change in color from green to pale yellow. A decrease in UV-Vis absorption and emission in the NIR region was observed only with H2 S. NIR-Lip1 and NIR-Lip2 are highly selective for H2 S with a LOD of 0.57 µM and 1.24 µM, respectively. It was observed that in a solid-like gel state, NIR-Lip1 is slightly more sensitive towards H2 S than fluid-like NIR-Lip2. The H2 S sensing mechanism was confirmed by ESI-mass and infrared (IR) spectroscopic analysis. Based on the high sensitivity and selectivity, NIR-Lip1 was employed to detect H2 S in vegetable samples. Further, the probes are found to be non-toxic and established for H2 S fluorescence imaging in live cells.

NLRP3 Inflammasome-Targeting Nanomicelles for Preventing Ischemia-Reperfusion-Induced Inflammatory Injury.

Ischemia-reperfusion (I/R) injury is a disease process that affects several vital organs. There is widespread agreement that the NLRP3 inflammasome pathway plays a crucial role in the development of I/R injury. We have developed transferrin-conjugated, pH-responsive nanomicelles for the entrapment of MCC950 drug. These nanomicelles specifically bind to the transferrin receptor 1 (TFR1) expressed on the cells of the blood-brain barrier (BBB) and thus help the cargo to cross the BBB. Furthermore, the therapeutic potential of nanomicelles was assessed using in vitro, in ovo, and in vivo models of I/R injury. Nanomicelles were injected into the common carotid artery (CCA) of a middle cerebral artery occlusion (MCAO) rat model to achieve maximum accretion of nanomicelles into the brain as blood flows toward the brain in the CCA. The current study reveals that the treatment with nanomicelles significantly alleviates the levels of NLRP3 inflammasome biomarkers which were found to be increased in oxygen-glucose deprivation (OGD)-treated SH-SY5Y cells, the I/R-damaged right vitelline artery (RVA) of chick embryos, and the MCAO rat model. The supplementation with nanomicelles significantly enhanced the overall survival of MCAO rats. Overall, nanomicelles exerted therapeutic effects against I/R injury, which might be due to the suppression of the activation of the NLRP3 inflammasome.

Light activated simultaneous release and recognition of biological signaling molecule carbon monoxide (CO).

The therapeutic action of carbon monoxide (CO) is very well known and has been studied on various types of tissues and animals. However, real-time spatial and temporal tracking and release of CO is still a challenging task. This paper reported an amphiphilic CO sensing probe NP and phospholipid 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) based nanoscale vesicular sensing system Ves-NP consisting of NP. The liposomal sensing system (Ves-NP) showed good selectivity and sensitivity for CO without any interference from other relevant biological analytes. Detection of CO is monitored by fluorescence OFF-ON signal. Ves-NP displayed LOD of 5.94 µM for CO detection with a response time of 5 min. Further, in a novel attempt, Ves-NP is co-embedded with the amphiphilic CO-releasing molecule 1-Mn(CO)3 to make an analyte replacement probe Ves-NP-CO. Having a both CO releasing and sensing moiety at the surface of the same liposomal system Ves-NP-CO play a dual role. Ves-NP-CO is used for the simultaneous release and recognition of CO that can be controlled by light. Thus, in this novel approach, for the first time we have attached both the release and recognition units of CO in the vesicular surface, both release and recognition simultaneously monitored by the change in fluorescent OFF-ON signal.

Caffeic Acid-Conjugated Budesonide-Loaded Nanomicelle Attenuates Inflammation in Experimental Colitis.

Ulcerative colitis is a multifactorial disease of the gastrointestinal tract which is caused due to chronic inflammation in the colon; it usually starts from the lower end of the colon and may spread to other portions of the large intestine, if left unmanaged. Budesonide (BUD) is a synthetically available second-generation corticosteroidal drug with potent local anti-inflammatory activity. The pharmacokinetic properties, such as extensive first-pass metabolism and quite limited bioavailability, reduce its therapeutic efficacy. To overcome the limitations, nanosized micelles were developed in this study by conjugating stearic acid with caffeic acid to make an amphiphilic compound. The aim of the present study was to evaluate the pharmacological potential of BUD-loaded micelles in a mouse model of dextran sulfate sodium-induced colitis. Micelles were formulated by the solvent evaporation method, and their physicochemical characterizations show their spherical shape under microscopic techniques like atomic force microscopy, transmission electron microscopy, and scanning electron microscopy. The in vitro release experiment shows sustained release behavior in physiological media. These micelles show cytocompatible behavior against hTERT-BJ cells up to 500 µg/mL dose, evidenced by more than 85% viable cells. BUD-loaded micelles successfully normalized the disease activity index and physical observation of colon length. The treatment with BUD-loaded micelles alleviates the colitis severity as analyzed in histopathology and efficiently, overcoming the disease severity via downregulation of various related cytokines (MPO, NO, and TNF-α) and inflammatory enzymes such as COX-2 and iNOS. Results of the study suggest that BUD-loaded nano-sized micelles effectively attenuate the disease conditions in colitis.

Lipid-encapsulated upconversion nanoparticle for near-infrared light-mediated carbon monoxide release for cancer gas therapy.

Cancer gas therapy is just in an early stage of research and development. Several important gasotransmitters have proven their therapeutic potentials, but handling, delivery and controlled release of these gases remain very challenging for therapeutic purposes. This research develops a versatile nanosystem that is capable of delivering carbon monoxide (CO) gasotransmitter in the form of photo-responsive carbon monoxide-releasing molecule (CORM) for targeted cancer therapy. The core-shell upconversion nanoparticles (UCNPs) were designed to transfer bio-friendly low energy near infrared (NIR) light to ultraviolet (UV) light and trigger CO release from the loaded CORM. The synthesized delivery system demonstrated its ability to mediate the sustained release of CO upon 808 or 980 nm NIR light excitation. The optimized nanoformulation was efficiently taken up by HCT116 cancer cells and showed dose-dependent cytotoxicity to HCT116 and other cancer cells. Intracellular CO release and subsequent therapeutic action involving ROS production were found to significantly contribute to cell apoptosis. Therefore, the current research demonstrates the potency and efficiency of an NIR-mediated UCNP-based CORM prodrug delivery system for targeted cancer gas therapy.

Sensing and Bioimaging of the Gaseous Signaling Molecule Hydrogen Sulfide by Near-Infrared Fluorescent Probes.

A fluorescent probe for the monitoring of H2S levels in living cells and organisms is highly desirable. In this regard, near-infrared (NIR) fluorescent probes have emerged as a promising tool. NIR-I and NIR-II probes have many significant advantages; for instance, NIR light penetrates deeper into tissue than light at visible wavelengths, and it causes less photodamage during biosample analysis and less autofluorescence, enabling higher signal-to-background ratios. Therefore, it is expected that fluorescent probes having emission in the NIR region are more suitable for in vivo imaging. Consequently, a considerable increase in reports of new H2S-responsive NIR fluorescent probes appeared in the literature. This review highlights the advances made in developing new NIR fluorescent probes aimed at the sensitive and selective detection of H2S in biological samples. Their applications in real-time monitoring of H2S in cells and in vivo for bioimaging of living cells/animals are emphasized. The selection of suitable dyes for designing NIR fluorescent probes, along with the principles and mechanisms involved for the sensing of H2S in the NIR region, are described. The discussions are focused on small-molecule and nanomaterials-based NIR probes.

Copper Complex-Embedded Vesicular Receptor for Selective Detection of Cyanide Ion and Colorimetric Monitoring of Enzymatic Reaction.

Detection of environmentally important ion cyanide (CN-) has been done by a new method involving displacement of both metal and indicator, metal indicator displacement approach (MIDA) on the vesicular interface. Terpyridine unit was selected as the binding site for metal (Cu2+), whereas Eosin-Y (EY) was preferred as an indicator. About 150 nm sized nanoscale vesicular ensemble (Lip-1.Cu) has shown good selectivity and sensitivity for CN- without any interference from other biologically and environmentally important anions. Otherwise, copper complexes are known for the interferences of binding with phosphates and amino acids. The Lip-1.Cu nanoreceptor also has the possibility to be used for real-time colorimetric scanning for the released HCN via enzymatic reactions. Lip-1.Cu has several superiorities over the other reported sensor systems. It has worked in 100% aqueous environment, fast response time with colorimetric monitoring of enzymatic reaction, and low detection limit.

Allosteric Regulation in Carbon Monoxide (CO) Release: Anion Responsive CO-Releasing Molecule (CORM) Derived from (Terpyridine)phenol Manganese Tricarbonyl Complex with Colorimetric and Fluorescence Monitoring.

A new CO-releasing terpyridine based manganese(I) tricarbonyl complex, [MnBr(CO)3(terpy-C6H4OH)] (1·Mn-OH) functioning via light has been reported. For the first time, we have demonstrated the allosteric regulation concept to control the CO-releasing properties of a CO-releasing molecule (CORM). Fluoride ion is reported to function as an allosteric activator to control the rate of CO release in the CORM. Complex 1·Mn-OH represents an interesting new class of CO-releasing system that releases CO upon irradiation with blue light (410 nm) over a period of 40 min with the half-time of 9.8 min. Fluoride ion selectively binds to the phenol moiety of the complex through hydrogen bonding and deprotonates to phenolate with a color change. Interestingly in the presence of fluoride ion, the rate of CO release is fast with the half-time of less than a minute. The rate of CO release is allosterically regulated by fluoride anion and can be monitored through a color change, fluorescence, and absorption based spectral changes along with IR studies and myoglobin assay.

Fluorescent nanoprobes for the sensing of gasotransmitters hydrogen sulfide (H2S), nitric oxide (NO) and carbon monoxide (CO).

Fluorescent nanomaterials as sensing probes have experienced immense growth in recent years due to the intrinsic optical and physicochemical properties, high sensitivity, specificity, targeting ability, and suitability for medicinal applications. The fluorescent detection of gaseous signaling molecules, such as Hydrogen sulfide (H2S), nitric oxide (NO) and carbon monoxide (CO) are very important due to their potential therapeutic application. This review intends to provide the recent progress in the detection of H2S, CO and NO via fluorescent based nano probes. These probes work based on different mechanisms such as fluorescence enhancement and quenching, also defined as "turn-on" and "turn-off" responses respectively. It could be achieved through PET, FRET or ratiometric methods. In this article, we have discussed about a variety of fluorescent nanoprobes of QDS, CDs, AuNPs and UCNPS, working on the fluorescent sensing mechanisms and applicable for the detection of H2S, CO and NO in biological and environmental samples. Methods used for the detection, structural features of nanomaterials, type of fluorescence response observed, fluorescence sensing mechanism and their sensitivity are highlighted.

Selective Detection of H2S by Copper Complex Embedded in Vesicles through Metal Indicator Displacement Approach.

A new approach for the detection of hydrogen sulfide (H2S) was constructed within vesicles comprising phospholipids and amphiphilic copper complex as receptor. 1,2-Distearoyl- sn-glycero-3-phosphocholine (DSPC) vesicles with embedded metal complex receptor (1.Cu) sites have been prepared. The vesicles selectively respond to H2S in a buffered solution and show colorimetric as well as spectral transformation. Other analytes such as reactive sulfur species, reactive nitrogen species, biological phosphates, and other anions failed to induce changes. The H2S detection is established through a metal indicator displacement (MIDA) process, where Eosin-Y (EY) was employed as an indicator. Fluorescence, UV-vis spectroscopy, and the naked eye as the signal readout studies confirm the high selectivity, sensitivity, and lower detection limit of the vesicular receptor. The application of vesicular receptors for real sample analysis was also confirmed by fluorescence live cell imaging.

Vesicles Functionalized with a CO-Releasing Molecule for Light-Induced CO Delivery.

In this paper, a new type of methodology to deliver carbon monoxide (CO) for biological applications has been introduced. An amphiphilic manganese carbonyl complex (1.Mn) incorporated into the 1,2-distearoyl-sn-glycero-3-phosphocholine lipid vesicles has been reported first time for the photoinduced release of CO. The liposomes (Ves-1.Mn) gradually released CO under light at 365 nm over a period of 50 min with a half-time of 26.5 min. The CO-releasing ability of vesicles appended with 1.Mn complexes has been confirmed by myoglobin assay and infrared study. The vesicles appended with 1.Mn have the advantages of biocompatibility, water solubility, and steady and slow CO release. This approach could be a rational approach for applying various water-insoluble photoinduced CO donors in aqueous media by using vesicles as a nanocarrier for CO release.

Reversible Colorimetric Sensor for Moisture Detection in Organic Solvents and Application in Inkless Writing.

Colorimetric sensors based on Sudan-III (1) and Alizarin red S (2) have been developed for the detection of a trace amount of water in organic solvents such as THF, acetone, acetonitrile, and DMSO. The deprotonated (anionic) forms of 1 and 2 namely 1.F and 2.F are reprotonated by using a trace amount of water. Deprotonation of 1 and 2 was obtained by using fluoride anion. Test papers of 1.F and 2.F in organic solvents with and without moisture showed dramatic changes in color. Receptor 1.F exhibits high sensitivity for water in acetone and THF with the detection limit as low as 0.0042 and 0.0058 wt %. Remarkably, probes 1.F and 2.F are reversible in nature both in solution and in test strips. 1.F and 2.F are reversible and reusable for sensing moisture in the organic solvents with high selectivity, high sensitivity, and fast response. The reversible moisture sensor 1.F has also been used for application in inkless writing.