Quantifying Y chromosome loss in primary and metastatic prostate cancer by chromosome painting.

Somatic Y chromosome loss in hematopoietic cells is associated with higher mortality in men. However, the status of the Y chromosome in cancer tissue is not fully known due to technical limitations, such as difficulties in labelling and sequencing DNA from the Y chromosome. We have developed a system to quantify Y chromosome gain or loss in patient-derived prostate cancer organoids. Using our system, we observed Y chromosome loss in 4 of the 13 (31%) patient-derived metastatic castration-resistant prostate cancer (mCRPC) organoids; interestingly, loss of Yq (long arm of the Y chromosome) was seen in 38% of patient-derived organoids. Additionally, potential associations were observed between mCRPC and Y chromosome nullisomy. The prevalence of Y chromosome loss was similar in primary and metastatic tissue, suggesting that Y chromosome loss is an early event in prostate cancer evolution and may not a result of drug resistance or organoid derivation. This study reports quantification of Y chromosome loss and gain in primary and metastatic prostate cancer tissue and lays the groundwork for further studies investigating the clinical relevance of Y chromosome loss or gain in mCRPC.

Surfactant-based supramolecular dye assembly: A highly selective and economically viable platform for quantification of heparin antidote.

Herein, we have employed a supramolecular assembly of a cationic dye, LDS-698 and a common surfactant sodium dodecyl sulfate (SDS) as a turn-on fluorescent sensor for protamine (Pr) detection. Addition of cationic Pr to the solution of dye-surfactant complex brings negatively charged SDS molecules together through strong electrostatic interaction, assisting aggregation of SDS way before its critical micellar concentration (CMC). These aggregates encapsulate the dye molecules within their hydrophobic region, arresting non-radiative decay channels of the excited dye. Thus, the LDS-698•SDS assembly displays substantial enhancement in fluorescence intensity that follows a nice linear trend with Pr concentration, providing limit of detection (LOD) for Pr as low as 3.84(±0.11) nM in buffer, 124.4(±6.7) nM in 1% human serum and 28.3(±0.5) nM in 100% human urine. Furthermore, high selectivity, low background signal, large stokes shift, and emission in the biologically favorable deep-red region make the studied assembly a promising platform for Pr sensing. As of our knowledge it is the first ever Pr sensory platform, using a very common surfactant (SDS), which is economically affordable and very easily available in the market. This innovative approach can replace the expensive, exotic and specialized chemicals considered for the purpose and thus showcase its potential in practical applications.

Quinaldine Red as a fluorescent probe for determining the melting temperature (Tm) of proteins: a simple, rapid and high-throughput assay.

Proteins play an important role in biological systems and several proteins are used in diagnosis, therapy, food industry etc. Thus, knowledge about the physical properties of the proteins is of utmost importance, which will aid in understanding their function and subsequent applications. The melting temperature (Tm) of a protein is one of the essential parameters which gives information about the stability of a protein under different conditions. In the present study, we have demonstrated a method for determining the Tm of proteins using the supramolecular interaction between Quinaldine Red (QR) and proteins. Using this method, we have determined the Tm of 5 proteins and compared our results with established protocols. Our results showed good agreement with the other methods and published values. The method developed in this study is inexpensive, quick, and devoid of complex instruments and pre/post-treatment of the samples. In addition, this method can be adopted for high throughput in multi-plate mode. Thus, this study projects a new methodology for Tm determination of various proteins with user friendly operation.

SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: a prospective cohort study and meta-analysis.

Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69-0.93), with little heterogeneity between studies (I2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy.

Trajectory tracking control of a pneumatically actuated continuum manipulator in the presence of obstacles by using terminal sliding mode control.

This paper proposes an efficient trajectory planning and dynamic tracking controller scheme for a pneumatic continuum manipulator under the effect of material hysteresis. First of all, generalized governing nonlinear dynamic equations in the form of partial differential equations for pneumatic continuum manipulator dynamics are developed by using discrete Cosserat-rod theory, where the manipulator material hysteresis is modeled by using a fractional order Bouc-Wen model. Then, the trajectory planning for the end-effector of a continuum manipulator is proposed, which accounts for the static obstacles in the workspace and the Jacobian singularity. Subsequently, an adaptive terminal sliding mode controller for the joint space control combined with a simple PI controller for task space control is proposed. The proposed controller guarantees exponential convergence of the manipulator tip positional error in finite time, even in the existence of external disturbances and model uncertainties, without any need for prior knowledge of their upper bounds. Finally, the proposed controller is applied to a two-segment continuum manipulator, the trunk of Robotino-XT, through numerical simulations and the performance gain over two controllers proposed in the literature for similar pneumatic continuum manipulators is demonstrated.

In house synthesized novel distyryl-BODIPY dye and polymer assembly as deep-red emitting probe for protamine detection.

In this contribution, we designed and synthesized a deep-red emitting distyryl-BODIPY dye (dye 3) which is non-fluorescent in aqueous solution due to the formation of non-emissive aggregates. However, in presence of an amphiphilic polymer (polystyrene sulfonate, PSS), the aggregated dye molecules de-aggregate and form dye 3-PSS complex, which significantly modulates the optical features of the bound dye. Interestingly, the dye 3-PSS complex shows turn-on fluorescence response in deep-red region in presence of protamine (Pr) due to the formation of dye 3-PSS-Pr ternary complex. Such enhancement follows a linear trend in the dynamic range of 0-8.75 µM of Pr which has been utilized to determine Pr with limit of detection (LOD) of 15.04(±0.5) nM in phosphate buffer. Furthermore, excellent selectivity of the dye 3-PSS system towards Pr allows us to determine Pr even in complex biological matrix like 1% human serum. Thus, dye 3-PSS system can be applied as a very effective tool for the detection and quantification of Pr in deep-red region, overcoming several limitations encountered with the probes in the shorter wavelength region. This is the first report on BODIPY dye based supramolecular assembly for sensing and quantification of protamine.

Polymer-mediated tuning of the monomer-aggregate equilibrium of a coumarin derivative for ratiometric sensing of protamine.

Amongst the various existing methods of analyte quantification, fluorescent-based methods, especially the ratiometric methods, continue to gain significant attention due to their high reproducibility, low environmental influence, and self-calibrating behavior. This paper presents the modulation in a monomer-aggregate equilibrium of coumarin-7 (C7) dye at pH ∼ 3, under the influence of a multi-anionic polymer, poly(styrene sulfonate) (PSS), leading to a significant modification in the ratiometric optical signal of the dye. At pH ∼ 3, cationic C7 formed aggregates in the presence of PSS via a strong electrostatic interaction, resulting in the development of a new emission peak at 650 nm at the expense of the monomer emission at 513 nm. Such contradicting changes in fluorescence intensities at two different wavelengths gave rise to a ratiometric signal, which was found to be highly sensitive towards external stimuli such as pH, and ionic strength. The stability of the C7-PSS complex was found to decrease as the pH of the solution was increased beyond 5, which indicated the decline in the electrostatic attraction between C7 and PSS due to the deprotonation of the C7 dye. Furthermore, an increase in the monomeric peak and a concomitant decrease of the aggregate peak with added salt in the solution (at pH ∼ 3) clearly justified the presence of an electrostatic attraction between C7 and PSS for the complex formation. This was further validated by the excited-state lifetime measurement of the C7-PSS complex, which showed a systematic increase in lifetime contribution from the monomeric species at the expense of aggregated species, as the concentration of NaCl increased in the solution. Thus, protamine (Pr), being a highly positively charged polypeptide, largely affected the monomer-aggregate equilibrium of the C7-PSS system, leading to a phenomenal change in the ratiometric signal, which was utilized to quantify with LOD as low as ∼2.8 nM in buffer for the bio-analyte Pr. Moreover, the ratiometric response of the C7-PSS assembly demonstrated excellent selectivity towards Pr, facilitating its practical relevance for the quantification of Pr in a 1% human serum matrix. Therefore, the studied C7-PSS can be utilized as a potential candidate for the quantification of the protamine even in complex biological media.

Optimal design of a helical coil support for dewars in fuel cell applications.

Fuel cells are gaining popularity because of their efficient energy production without causing environmental pollution. Recently, DRDO has developed a fuel cell-based air-independent propulsion (AIP) system. In this system, the hydrogen is produced onboard while oxygen is carried in liquefied form (LOX) from the land in specially designed insulated storage vessels called dewars. Such vessels are needed because LOX has a low boiling point (NBP ~ 90 K) and heat of vaporization (~ 213 kJ/kg), due to which it boils off easily even when there is a small amount of heat inleak from the ambient. A typical dewar consists of two vessels separated by insulation. Support members are used to hold the two vessels together. Heat inleak through the supports and the insulation of the dewar causes the boiling of LOX. The vessels are subjected to dynamic loads during the voyage due to the filling and consumption of LOX. Therefore, the support system should be designed to withstand the dynamic loads experienced by the dewar. While the support system should have enough mechanical strength to withstand the loads it is subjected to, it should also restrict the heat inleak from the ambient to minimize the LOX boil-off. To meet this requirement, we need to optimize the support system design. Design optimization of support systems is especially critical in submarines to reduce the snorkeling frequency. Even though the dewars are available commercially for various applications, their design methodologies are not available in the open literature. Cylindrical rods are generally used as support members. In earlier studies, the authors have shown that helical coils give better thermal performance than tension rods as dewar supports. These two support systems involve different design criteria. It is important to evolve an optimal design of the support system to maximize the mechanical strength of the support while minimizing the heat inleak through the support. In this paper, we present a design methodology for optimizing helical support. We have proposed a modified optimization technique derived from the classical genetic algorithm (GA) for this purpose. The modification has been done by ensuring the design feasibility of the coil at each step of the algorithm. The proposed optimization technique has been tested on a LOX dewar, and an optimal design of the helical coil support has been obtained.

Grading of HCC Biopsy Images Using Nucleus and Texture Features.

Hepatocellular carcinoma (HCC) is one of the most critical health problems in the world. For proper treatment, it is important to identify the grade of cancer morbidity from HCC biopsy image. The diagnostic work is not only time-consuming but also subjective. The same biopsy image may be diagnosed as of different grades by different doctors, due to lack of experience or difference in opinion. In this work, we proposed an automatic grading system with classification accuracy matching to an experienced doctor, to help augment the diagnosis process. First, we proposed a segmentation method to isolate all nucleus-like objects present in a biopsy image. Non-target objects (here the target is a single HCC nucleus) present in the biopsy image are isolated too in the segmentation process. To eliminate such non-target objects, we proposed clustering of segmented images and a novel method to filter out target objects. Next, we proposed a two track neural network, where input consists of 2 different images. It combines a single segmented nucleus and a random cropped texture patch of the biopsy image to which the nucleus belongs. At this classifier output, we grade the single nucleus. Finally, a majority voting method is used to identify the grade of the whole biopsy image. We achieved an accuracy of 99.03% for nucleus image grading and 99.66% accuracy for grading biopsy images.

Fluorogenic gemcitabine based light up sensor for serum albumin detection in complex biological matrices.

Herein we report fluorogenic derivative of gemcitabine (GEM-DNS), synthesized from gemcitabine hydrochloride and dansyl chloride in a single step. Owing to its large stoke shift of ∼200 nm and intriguing photophysical properties, the said dye has been utilized to estimate albumin concentration in complex bio-media such as human urine and blood serum. High sensitivity and selectivity towards albumin make the aforementioned dye a powerful diagnostic tool to detect ailments such as liver cirrhosis, diabetes, hypertension etc.

Increased MYBL2 expression in aggressive hormone-sensitive prostate cancer.

Loss of the histone demethylase KDM5D (lysine-specific demethylase 5D) leads to in vitro resistance of prostate cancer cells to androgen deprivation therapy (ADT) with and without docetaxel. We aimed to define downstream drivers of the KDM5D effect. Using chromatin immunoprecipitation sequencing (ChIP-seq) of the LNCaP cell line (androgen-sensitive human prostate adenocarcinoma) with and without silenced KDM5D, MYBL2-binding sites were analyzed. Associations between MYBL2 mRNA expression and clinical outcomes were assessed in cohorts of men with localized and metastatic hormone-sensitive prostate cancer. In vitro assays with silencing and overexpression of MYBL2 and KDM5D in androgen receptor (AR)-positive hormone-sensitive prostate cancer cell lines, LNCaP and LAPC4, were used to assess their influence on cellular proliferation, apoptosis, and cell cycle distribution, as well as sensitivity to androgen deprivation, docetaxel, and cabazitaxel. We found that silencing KDM5D increased histone H3 lysine K4 (H3K4) trimethylation and increased MYBL2 expression. KDM5D and MYBL2 were negatively correlated with some but not all clinical samples. Higher MYBL2 expression was associated with a higher rate of relapse in localized disease and poorer overall survival in men with metastatic disease in the CHAARTED trial. Lower MYBL2 levels enhanced LNCaP and LAPC4 sensitivity to androgen deprivation and taxanes. In vitro, modifications of KDM5D and MYBL2 altered cell cycle distribution and apoptosis in a cell line-specific manner. These results show that the transcription factor MYBL2 impacts in vitro hormone-sensitive prostate cancer sensitivity to androgen deprivation and taxanes, and lower levels are associated with better clinical outcomes in men with hormone-sensitive prostate cancer.

Red emitting fluorogenic dye as an efficient turn-on probe for milk allergen.

Development of simple, fast and non-destructive technique such as fluorescence based method for the quantification of milk allergens in various dairy products is a highly rewarding task. In this contribution, a red emitting fluorogenic dye, quinaldine red (QR) is reported for the detection and quantification of a milk allergen, beta lactoglobulin (ß-LG) in milk and whey matrices, utilizing its high selectivity and sensitivity towards ß-LG. Detail spectroscopic investigation reveals that binding of QR to the hydrophobic calyx site of ß-LG protein substantially reduces the torsional agility and propensity of TICT state formation of QR, rendering the dye highly fluorescent in nature. This enables estimation of ß-LG with LOD 52.1(±0.9) nM in buffer solution and 0.21(±0.01) µM in 5 % bovine milk matrix respectively. Additionally, high selectivity and sensitivity, excellent repeatability, quick response, and emission in the biologically favorable red spectral region make QR based fluorometric quantification of ß-LG a highly attractive choice. Finally, the estimated ß-LG concentrations in milk and whey matrices from fluorometric titration and densitometry methods are found to match excellently with each other, suggesting potential of QR as an efficient turn-on fluorescent probe for the quantification of ß-LG (milk allergen) in various dairy products.

The Impact of PIK3R1 Mutations and Insulin-PI3K-Glycolytic Pathway Regulation in Prostate Cancer.

PURPOSE: Oncogenic alterations of the PI3K/AKT pathway occur in >40% of patients with metastatic castration-resistant prostate cancer, predominantly via PTEN loss. The significance of other PI3K pathway components in prostate cancer is largely unknown. EXPERIMENTAL DESIGN: Patients in this study underwent tumor sequencing using the MSK-IMPACT clinical assay to capture single-nucleotide variants, insertions, and deletions; copy-number alterations; and structural rearrangements, or were profiled through The Cancer Genome Atlas. The association between PIK3R1 alteration/expression and survival was evaluated using univariable and multivariable Cox proportional-hazards regression models. We used the siRNA-based knockdown of PIK3R1 for functional studies. FDG-PET/CT examinations were performed with a hybrid positron emission tomography (PET)/CT scanner for some prostate cancer patients in the MSK-IMPACT cohort. RESULTS: Analyzing 1,417 human prostate cancers, we found a significant enrichment of PIK3R1 alterations in metastatic cancers compared with primary cancers. PIK3R1 alterations or reduced mRNA expression tended to be associated with worse clinical outcomes in prostate cancer, particularly in primary disease, as well as in breast, gastric, and several other cancers. In prostate cancer cell lines, PIK3R1 knockdown resulted in increased cell proliferation and AKT activity, including insulin-stimulated AKT activity. In cell lines and organoids, PIK3R1 loss/mutation was associated with increased sensitivity to AKT inhibitors. PIK3R1-altered patient prostate tumors had increased uptake of the glucose analogue 18F-fluorodeoxyglucose in PET imaging, suggesting increased glycolysis. CONCLUSIONS: Our findings describe a novel genomic feature in metastatic prostate cancer and suggest that PIK3R1 alteration may be a key event for insulin-PI3K-glycolytic pathway regulation in prostate cancer.

Mesenchymal and stem-like prostate cancer linked to therapy-induced lineage plasticity and metastasis.

Bioinformatic analysis of 94 patient-derived xenografts (PDXs), cell lines, and organoids (PCOs) identifies three intrinsic transcriptional subtypes of metastatic castration-resistant prostate cancer: androgen receptor (AR) pathway + prostate cancer (PC) (ARPC), mesenchymal and stem-like PC (MSPC), and neuroendocrine PC (NEPC). A sizable proportion of castration-resistant and metastatic stage PC (M-CRPC) cases are admixtures of ARPC and MSPC. Analysis of clinical datasets and mechanistic studies indicates that MSPC arises from ARPC as a consequence of therapy-induced lineage plasticity. AR blockade with enzalutamide induces (1) transcriptional silencing of TP53 and hence dedifferentiation to a hybrid epithelial and mesenchymal and stem-like state and (2) inhibition of BMP signaling, which promotes resistance to AR inhibition. Enzalutamide-tolerant LNCaP cells re-enter the cell cycle in response to neuregulin and generate metastasis in mice. Combined inhibition of HER2/3 and AR or mTORC1 exhibits efficacy in models of ARPC and MSPC or MSPC, respectively. These results define MSPC, trace its origin to therapy-induced lineage plasticity, and reveal its sensitivity to HER2/3 inhibition.

Molecular Imaging of Neuroendocrine Prostate Cancer by Targeting Delta-Like Ligand 3.

Treatment-induced neuroendocrine prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer. Using the 89Zr-labeled delta-like ligand 3 (DLL3) targeting antibody SC16 (89Zr-desferrioxamine [DFO]-SC16), we have developed a PET agent to noninvasively identify the presence of DLL3-positive NEPC lesions. Methods: Quantitative polymerase chain reaction and immunohistochemistry were used to compare relative levels of androgen receptor (AR)-regulated markers and the NEPC marker DLL3 in a panel of prostate cancer cell lines. PET imaging with 89Zr-DFO-SC16, 68Ga-PSMA-11, and 68Ga-DOTATATE was performed on H660 NEPC-xenografted male nude mice. 89Zr-DFO-SC16 uptake was corroborated by biodistribution studies. Results: In vitro studies demonstrated that H660 NEPC cells are positive for DLL3 and negative for AR, prostate-specific antigen, and prostate-specific membrane antigen (PSMA) at both the transcriptional and the translational levels. PET imaging and biodistribution studies confirmed that 89Zr-DFO-SC16 uptake is restricted to H660 xenografts, with background uptake in non-NEPC lesions (both AR-dependent and AR-independent). Conversely, H660 xenografts cannot be detected with imaging agents targeting PSMA (68Ga-PSMA-11) or somatostatin receptor subtype 2 (68Ga-DOTATATE). Conclusion: These studies demonstrated that H660 NEPC cells selectively express DLL3 on their cell surface and can be noninvasively identified with 89Zr-DFO-SC16.

Waste derived approach towards wealthy fluorescent N-doped graphene quantum dots for cell imaging and H2O2 sensing applications.

Herein, we report the synthesis of a highly fluorescent nitrogen doped graphene quantum dots (N-GQDs) from waste precursors such as melamine sponge and arjuna bark via a microwave treatment and its functional and morphological characterization using various spectroscopy techniques such as optical, FTIR, XPS and TEM. The as-prepared aqueous N-GQD (dia. 2-3 nm) was used for the bio-imaging application using breast carcinoma cell line (MDA-MB-231) as a model, and the locations of all cells in the cytoplasm as well as nuclei were observed to stain brightly in blue fluorescent color successfully. In addition to that, the aqueous N-GQD showed fluorescence quenching behavior in the presence of hydrogen peroxide, which was exploited to sense H2O2, a probable toxin generated in the diseased cells. Importantly, the cell cytotoxicity was measured and found to be non-toxic (70% survival) to the MDA-MB-231 cells even at very high concentration (∼1.8 mg/ml) of the synthesized N-GQD. This study revealing excellent biocompatibility and imaging of the model cancer cells, and sensing of H2O2 by fluorescent quenching, indicates potential in-vivo cell culture applications of the prepared fluorescent N-GQD.

Prognostic and therapeutic significance of COP9 signalosome subunit CSN5 in prostate cancer.

Chromosome 8q gain is associated with poor clinical outcomes in prostate cancer, but the underlying biological mechanisms remain to be clarified. CSN5, a putative androgen receptor (AR) partner that is located on chromosome 8q, is the key subunit of the COP9 signalosome, which deactivates ubiquitin ligases. Deregulation of CSN5 could affect diverse cellular functions that contribute to tumor development, but there has been no comprehensive study of its function in prostate cancer. The clinical significance of CSN5 amplification/overexpression was evaluated in 16 prostate cancer clinical cohorts. Its oncogenic activity was assessed by genetic and pharmacologic perturbations of CSN5 activity in prostate cancer cell lines. The molecular mechanisms of CSN5 function were assessed, as was the efficacy of the CSN5 inhibitor CSN5i-3 in vitro and in vivo. Finally, the transcription cofactor activity of CSN5 in prostate cancer cells was determined. The prognostic significance of CSN5 amplification and overexpression in prostate cancer was independent of MYC amplification. Inhibition of CSN5 inhibited its oncogenic function by targeting AR signaling, DNA repair, multiple oncogenic pathways, and spliceosome regulation. Furthermore, inhibition of CSN5 repressed metabolic pathways, including oxidative phosphorylation and glycolysis in AR-negative prostate cancer cells. Targeting CSN5 with CSN5i-3 showed potent antitumor activity in vitro and in vivo. Importantly, CSN5i-3 synergizes with PARP inhibitors to inhibit prostate cancer cell growth. CSN5 functions as a transcription cofactor to cooperate with multiple transcription factors in prostate cancer. Inhibiting CSN5 strongly attenuates prostate cancer progression and could enhance PARP inhibition efficacy in the treatment of prostate cancer.

Carbon nano-dot for cancer studies as dual nano-sensor for imaging intracellular temperature or pH variation.

Cellular temperature and pH govern many cellular physiologies, especially of cancer cells. Besides, attaining higher cellular temperature plays key role in therapeutic efficacy of hyperthermia treatment of cancer. This requires bio-compatible, non-toxic and sensitive probe with dual sensing ability to detect temperature and pH variations. In this regard, fluorescence based nano-sensors for cancer studies play an important role. Therefore, a facile green synthesis of orange carbon nano-dots (CND) with high quantum yield of 90% was achieved and its application as dual nano-sensor for imaging intracellular temperature and pH was explored. CND was synthesized from readily available, bio-compatible citric acid and rhodamine 6G hydrazide using solvent-free and simple heating technique requiring purification by dialysis. Although the particle size of 19 nm (which is quite large for CND) was observed yet CND exhibits no surface defects leading to decrease in photoluminescence (PL). On the contrary, very high fluorescence was observed along with good photo-stability. Temperature and pH dependent fluorescence studies show linearity in fluorescence intensity which was replicated in breast cancer cells. In addition, molecular nature of PL of CND was established using pH dependent fluorescence study. Together, the current investigation showed synthesis of highly fluorescent orange CND, which acts as a sensitive bio-imaging probe: an optical nano-thermal or nano-pH sensor for cancer-related studies.

Host-Assisted Aggregation-Induced Emission of a Tetraphenylethylene Derivative and Its Responses toward External Stimuli.

Aggregation-induced emission (AIE) of fluorogenic dyes offers many opportunities as smart materials, fluorescence sensing of analytes, bioimaging, molecular electronics, and many others. AIE dyes (called AIEgens) produce emission through aggregation, which are more advantageous than conventional emission of monomeric fluorophores, as the latter is unduly susceptible toward various quenching processes. Here, we report AIE enhancement of a polyanionic sulfonato-tetraphenylethylene (SuTPE) derivative, achieved through supramolecularly assisted dye aggregation, as SuTPE interacts with a multicationic amino-ß-cyclodextrin (AßCD) host. Aggregation of the dye is induced mainly because of strong electrostatic interaction of SuTPE with AßCD, causing a significant extent of charge neutralization for the polyanionic dyes, helping their assemblage at the multicationic host portal. Job's plot studies suggest preferential formation of 2:1 dye-to-host stoichiometric complexes in the present system. Ionic-strength-dependent studies nicely support the involvement of electrostatic interaction in the present system through salt-induced disintegration of the SuTPE-AßCD complexes. The AIE enhancement for the SuTPE-AßCD system is very sensitive to the external stimuli, such as pH and temperature, suggesting its prospects in various stimuli-responsive applications. Furthermore, the SuTPE-AßCD system can suitably quantify an important bioanalyte, ATP, following a competitive binding strategy, suggesting its potential application as a supramolecular biosensor.